| 1. |
- Al-Hawasi, Abbas, 1976-
(författare)
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Retinal ganglion cell examination with Optical Coherence Tomography reflects physiological and pathological changes in the eye and the brain.
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The retinal ganglion cell is situated in the inner retina and its axons, composing the retinal nerve fiber layer (RNFL), leave the eye to form the optic nerve. These cells develop embryologically from the forebrain and later during development re-establish connections with different parts of the brain serving different purposes. This unique position and connections make it possible to be investigated with different methods. Optical Coherence Tomography (OCT) is an accessible and easily operated clinical device that can provide a detailed image of this layer at a few micrometers level of precision in measurements. In this thesis we aimed to see whether examining these cells with OCT could reflect physiological and pathological changes in the eye and brain.In cases of optic neuritis (Paper I), the OCT examination showed early thickening of the peripapillary (pRNFL) followed by thinning which takes 6-9 months to reduce to below normal thickness without the ability to distinguish between the real from pseudo thinning. The ganglion cell -inner plexiform layer (GCL-IPL) layer, however, showed a thickness reduction within a few weeks to 3 months without pseudo thinning. In cases of Idiopathic Intracranial Hypertension (IIH) (Paper II), the GCL-IPL remained unchanged and there was no difference in pRNFL thickness compared to healthy controls, whereas the optic disc parameters of rim thickness, rim area, cup volume and cup/disc ratio differed significantly (P<0.05).In cases of benign multiple sclerosis (Paper IV), the OCT could detect that eyes which are not affected by optic neuritis had an annual thinning rate of the RNFL and GCL-IPL similar to a healthy population (P>0.05) which may indicate the benign course of the disease. In cases of physiological factors affecting the GCL in healthy population (Paper III) the OCT examination showed that there was a significant thinning rate of the layer with age (P<0.05), but the thinning was not significant when sex and axial length of the eye were taken into consideration. Males had a thicker GCL volume than females and with age a significant reduction in GCL volume was noted in females but not in males. A Longer axial length of the eye found to be associated with thinner GCL volume. In conclusion retinal ganglion cell changes detected with OCT can reflect physiological and pathological changes in the eye and brain.
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| 2. |
- Bourghardt Peebo, Beatrice, 1968-, et al.
(författare)
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Expression of the focal adhesion protein PINCH in normal and alkali-injured corneas and the role of PMNs
- 2007
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Ingår i: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907 .- 1600-0420. ; 85:4, s. 395-400
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To evaluate the role of particularly interesting new cysteine-histidine-rich protein (PINCH) in corneal wound healing and early neovascularization and to assess the influence of granulocytes. Methods: A standardized corneal alkali wound was inflicted under general anaesthesia to the right eye of 14 New Zealand White rabbits. Seven of the rabbits received i.v. 5 mg/kg fucoidin every 2 hours to prevent granulocytes from entering the wound area. After 36 hours, the rabbits were killed, the corneas excised, fixed in 4% formaldehyde and embedded in paraffin. The sections were double-stained with antibodies against PINCH and with haematoxylin. Results: In the normal cornea and limbus, PINCH was weakly expressed in the corneal epithelium and in a wedge of the conjunctival stroma. In the wounded corneas, PINCH expression was seen in the frontline of repopulating endothelial and epithelial cells, and in active keratocytes. The vascular endothelium and the granulocytes expressed PINCH, as did the conjunctival epithelium. In the fucoidin-treated rabbits, PINCH expression was markedly reduced. The vascular endothelial cells and the few granulocytes did not express PINCH in these rabbits. Conclusions: PINCH is only slightly expressed in the normal cornea. A corneal wound induces PINCH expression in the repopulating cells, in the vascular endothelial cells of the limbus, in the limbal epithelium and in the granulocytes. Exclusion of granulocytes reduces expression of PINCH and there is no expression at all in the vascular endothelium. © 2007 The Authors Journal compilation 2007 Acta Ophthalmol Scand.
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| 3. |
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| 5. |
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| 6. |
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| 7. |
- Fagerholm, Per, 1948-, et al.
(författare)
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Epithelial ingrowth after LASIK treatment with scraping and phototherapeutic keratectomy
- 2004
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Ingår i: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907 .- 1600-0420. ; 82:6, s. 707-713
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To evaluate the effect of phototherapeutic keratectomy (PTK) in combination with manual scraping when removing epithelial ingrowth under a LASIK flap.Material and Methods: Three patients, who had undergone several surgeries following LASIK in order to remove epithelial ingrowth that was threatening vision, were treated with a flap lift, manual abrasion and PTK. The PTK was performed on both the stromal and the flap side with the aim of eliminating the threat and improving vision. Two patients underwent primary surgery to remove epithelial ingrowth with manual abrasion and PTK. The influence on vision, topography and cell recurrences was evaluated.Results: Uncorrected visual acuity (UCVA) and best spectacle-corrected visual acuity (BSCVA) improved in four cases and remained good in the fifth case. The refraction did not change significantly. Topography disclosed changes in the irregular astigmatism, explaining the improved BSCVA. Central epithelial ingrowth did not recur, whereas peripheral ingrowth did. The peripheral ingrowth did not progress, except in case 1, where a cyst formed that required surgery.Conclusions: It is our belief that adding PTK to manual scraping improves the prognosis for eyes with epithelial ingrowth. It is mainly the central ingrowth that is positively affected. Improved adhesion between the stroma and the flap is one possible explanation.
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| 8. |
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| 9. |
- Fagerholm, Per, 1948-, et al.
(författare)
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Inherited corneal opacifications with an unusual distribution
- 2007
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Ingår i: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907 .- 1600-0420. ; 85:1, s. 103-105
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To describe corneal opacities of a new type and distribution in a small family. Methods: Family members were interviewed and examined to establish a pedigree and to detect any corneal abnormalities. Results: Two family members presented with corneal opacities. Both had, in the very peripheral cornea, flat, greyish, rounded opacities, 20-200μm in diameter, on the Descemet's membrane. In addition, the mother had the same type of opacities over the central cornea just inside the Bowman's layer. The remaining parts of the corneas were clear. Vision was unaffected and the opacities caused no discomfort. There was no other corneal pathology. The subjects' general health was good. Conclusions: To our knowledge, these types and distribution of corneal opacities have not been described previously. Although the mode of inheritance at this point is uncertain, we believe the changes are of a dystrophic nature. © 2007 Acta Ophthalmol Scand.
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| 10. |
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| 11. |
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| 12. |
- Fagerholm, Per, 1948-
(författare)
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Phototherapeutic keratectomy : 12 years of experience
- 2003
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Ingår i: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907 .- 1600-0420. ; 81:1, s. 19-32
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Tidskriftsartikel (refereegranskat)abstract
- Background: Phototherapeutic keratectomy (PTK) has been employed as a surgical tool to treat corneal disease for more than 10 years. The laser has made it possible to remove superficial corneal opacities and thereby restore vision. The 193 nm ultraviolet light separates molecules and splits molecules in biological tissue, thereby ablating it. About 0.25 ╡m of tissue is ablated by each pulse. The development of the excimer laser technique has been fast. It has principally focused on refractive surgery but has also benefited PTK. Corneal dystrophies: The ability to delay or postpone corneal grafting in superficial corneal dystrophies represents a very important achievement. Map-dot-fingerprint dystrophy or basal membrane dystrophy is a common indication for PTK. Other dystrophies such as Meesman's, Reis-Bⁿckler's, Thiel-Benke's, granular, macular, lattice and Schnyder's can be treated, although with differing degrees of success and varying rates of recurrence. Subepithelial scarring in Fuchs' dystrophy has been ablated. Other trials have involved the removal of substantial parts of the stroma in order to reduce the load on the endothelium. Recurrent dystrophic changes can likewise be removed from corneal grafts and thus prevent the need for regrafting. Recurrent erosions: Laser treatment has made it possible to manage wound-healing problems better after recurrent erosions. Recurrent erosions are the most common indications for PTK: several studies show good and persistent effects with this type of treatment. Persistent epithetial defects of various origins, among them corneal ulcers resulting from allergic disease, can likewise be treated. Scar tissue: Scars after surgery such as pterygeum excision can be removed. Smooth muscle actin containing fibroblasts in old scars should be given special consideration in PTK. Excimer laser surgery can be successfully combined with conventional surgery to remove excessive scar tissue, Salzmann's nodules and very flaky and coarse band keratopathy. Irregular corneal surfaces following ulcers and injuries pose problems that have so far proved difficult to overcome. Thinning is often seen after bacterial corneal ulcers or after herpes simplex keratitis. A rough or uneven surface can be made smoother by using modulators during treatment by casting a new surface under a hard contact lens (PALM technique), a surface that is then projected into the stroma by laser ablation. Modern techniques linking the excimer laser with computerized corneal topography and wavefront analysis promise to further improve the smoothing capacities of lasers and to increase the quality of optical results. Complications: The most feared complication of PTK is the postoperative infection. These are rare. Haze is usually not prominent but scar tissue formation of a more persistent type has been noted after laser surgery in eyes with pre-existing surgical scars. Keratectasia has been described after PTK. Failure due to deep opacities or a surface that is too uneven is a more common frustration. This paper reviews advances in excimer laser treatment of corneal disease.
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| 13. |
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| 14. |
- Fagerholm, Per, 1948-, et al.
(författare)
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Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 in the regulation of corneal neovascularization and wound healing
- 2004
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Ingår i: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907 .- 1600-0420. ; 82:5, s. 557-563
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To study the change in expression of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 in the rabbit cornea and limbus following a penetrating, central corneal alkali burn. The influence of different cells on VEGF and VEGFR-2 expression was studied by excluding granulocytes from the wound area. Methods: Fourteen New Zealand white rabbits were subjected to a penetrating, 5-mm diameter, central corneal alkali burn in one eye under general anaesthesia. Seven of the rabbits were given injections of fucoidin for 36 hours. The rabbits were killed after 36 hours and the corneas were excised with a sclera rim and prepared for immunohistochemistry. Results: Both VEGF and VEGFR-2 are strongly expressed in the frontline of repopulating epithetial, stromal and endothelial cells during wound healing, irrespective of granulocyte presence. Vascular endothelial cells express VEGF strongly after injury, but only in the presence of granulocytes. Conclusion: Corneal neovascularization requires the presence of granulocytes to stimulate vascular endothelial cells. During wound healing in this area, VEGF is a factor that stimulates proliferation and migration and that is not influenced by granulocytes.
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| 15. |
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| 16. |
- Gan, Lisha, 1957-, et al.
(författare)
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Cellular proliferation and leukocyte infiltration in the rabbit cornea after photorefractive keratectomy
- 2001
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Ingår i: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907 .- 1600-0420. ; 79:5, s. 488-492
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To map the proliferative activity of corneal cells during wound healing following photorefractive keratectomy (PRK) and to compare two markers for proliferation. Methods: PRK, 5- mm in diameter with a -6 D setting, was performed in one eye of 28 New Zealand White Rabbits. The rabbits were sacrificed at time points between 12 hours and three months after surgery. The treated and fellow corneas were fixed in 10% formaldehyde, paraffin embedded, and immunohistochemically stained for proliferate cell nuclear antigen (PCNA) and at one time point, 1 week, also for Ki-67. Results: Following initial sliding of the epithelial cells, the proliferative activity in the wound area starts in the leading edge (24 hours) and is spread towards the periphery. The proliferative activity peaks after one week and subsides during the following two weeks. Early (24 hours) proliferative activity is also seen in the limbal epithelium which peaks after three days. The keratocytes express PCNA in the peripheral stroma 48 hours after injury. They then also migrate to repopulate the stroma under the wound area. The expression period lasts 1 week and subsides the following week. Leukocytes are found in the wound as early as 12 hours after injury. The cells disappear around the time of epithelial wound closure, i.e. after 3 days. The two proliferative markers PCNA and KI 67 show a similar distribution after surgery. Conclusion: Epithelial proliferative activity starts earlier after injury, and is preceded by leukocyte presence in the wound. The PCNA expression starts later in the keratocytes but lasts somewhat longer (3 weeks). PCNA expression appears more efficient than Ki-67 to show proliferative activity of slow cycling cells in the cornea.
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| 17. |
- Gan, Lisha, 1957-, et al.
(författare)
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Expression of basic fibroblast growth factor in rabbit corneal alkali wounds in the presence and absence of granulocytes
- 2005
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Ingår i: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907 .- 1600-0420. ; 83:3, s. 374-378
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To study the expression of basic fibroblast growth factor (bFGF) in the early phases of corneal wound healing in the presence or absence of granulocytes. Methods: A central penetrating corneal alkali wound was inflicted to one eye in each of 14 rabbits under general anaesthesia. Subsequently, seven of the rabbits were given fucoidin i.v. for 36 hours in order to block the selectins on the vascular endothelium, thus preventing blood granulocytes from entering the tissues. Then, corneas were prepared, stained for bFGF and evaluated by light microscopy. Results: Whereas normal corneal epithelium expressed bFGF weakly, conjunctival epithelium did so strongly, particularly the goblet cells. The corneal endothelium showed medium staining, while keratocytes and vascular endothelial cells did not consistently express bFGF. After 36 hours of wound healing, a marked upregulation of bFGF expression was observed in the corneal epithelial and endothelial cells, as well as in the keratocytes, that were migrating into the wound. No other changes were noted. None of these features were modulated when granulocyte emigration was prevented by fucoidin administration. Conclusions: The difference in bFGF expression between the corneal and conjunctival epithelium suggests a role for this growth factor in the barrier function at the limbus. Moreover, the specific presence of bFGF in cells migrating into the wound indicates the participation of bFGF in corneal wound healing. Expression of bFGF was independent of granulocytes. Copyright © Acta Ophthalmol Scand 2005.
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| 18. |
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| 19. |
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| 20. |
- Islam, Mohammad Mirazul, 1984-, et al.
(författare)
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Biomaterials-enabled cornea regeneration in patients at high risk for rejection of donor tissue transplantation
- 2018
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Ingår i: NPJ Regenerative medicine. - : Springer Science and Business Media LLC. - 2057-3995. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- The severe worldwide shortage of donor organs, and severe pathologies placing patients at high risk for rejecting conventional cornea transplantation, have left many corneal blind patients untreated. Following successful pre-clinical evaluation in mini-pigs, we tested a biomaterials-enabled pro-regeneration strategy to restore corneal integrity in an open-label observational study of six patients. Cell-free corneal implants comprising recombinant human collagen and phosphorylcholine were grafted by anterior lamellar keratoplasty into corneas of unilaterally blind patients diagnosed at high-risk for rejecting donor allografts. They were followed-up for a mean of 24 months. Patients with acute disease (ulceration) were relieved of pain and discomfort within 1-2 weeks post-operation. Patients with scarred or ulcerated corneas from severe infection showed better vision improvement, followed by corneas with burns. Corneas with immune or degenerative conditions transplanted for symptom relief only showed no vision improvement overall. However, grafting promoted nerve regeneration as observed by improved touch sensitivity to near normal levels in all patients tested, even for those with little/no sensitivity before treatment. Overall, three out of six patients showed significant vision improvement. Others were sufficiently stabilized to allow follow-on surgery to restore vision. Grafting outcomes in mini-pig corneas were superior to those in human subjects, emphasizing that animal models are only predictive for patients with non-severely pathological corneas; however, for establishing parameters such as stable corneal tissue and nerve regeneration, our pig model is satisfactory. While further testing is merited, we have nevertheless shown that cell-free implants are potentially safe, efficacious options for treating high-risk patients.
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| 21. |
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| 22. |
- Koulikovska, Marina, 1970-, et al.
(författare)
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Platelet Rich Plasma Prolongs Myofibroblast Accumulation in Corneal Stroma with Incisional Wound
- 2015
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Ingår i: Current Eye Research. - : Taylor & Francis. - 0271-3683 .- 1460-2202. ; 40:11, s. 1102-1110
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The purpose of this study was to determine whether platelet rich plasma (PRP) has an effect on corneal stromal cells in a rat model of wound healing following corneal incision. Materials and Methods: The effect of PRP on corneal wound healing in vivo was investigated in a corneal incision wound model in rats. 40 rats were wounded by deep corneal incision, and treated with either topically administered PRP (20 rats) or sodium chloride (20 rats). At 4 hours and 1, 3, and 5 days after incision, α-smooth muscle actin (α SMA), SMAD2 and SMAD3 expression and apoptosis in stromal cells were evaluated by immunohistochemistry, and IL-1β mRNA expression was evaluated by real time PCR.Results: PRP treated corneas exhibited reduced stromal cell apoptosis at day 3 and day 5 (p = 0.038, and <0.001, respectively) relative to controls. Interleukin-1β mRNA expression, however, was unchanged in PRP treated corneas relative to controls. Topical PRP treatment resulted in a higher proportion of αSMA-positive myofibroblasts recruited to the wound site relative to control corneas. PRP did not affect activation of SMAD2 but activation of SMAD3 was significantly reduced at day 1 (p=0.001) and dramatically increased at day 5 (p=0.032).Conclusions: PRP treatment resulted in suppressed stromal cell apoptosis followed by SMAD3 activation and a greater proportion of myofibroblasts present at the wound site. Suppression of stromal cell apoptosis after corneal wounding by use of a growth factor rich formulation may lead to myofibroblast accumulation by modulation of the TGF-β pathway.
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| 23. |
- Koulikovska, Marina, 1970-, et al.
(författare)
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The expression pattern of the subunit of chaperonin containing T-complex polypeptide 1 and its substrate, α-smooth muscle actin, during corneal wound healing
- 2005
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Ingår i: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907 .- 1600-0420. ; 83:5, s. 543-548
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: This study was designed to demonstrate the expression of the chaperonin containing T-complex polypeptide 1 (CCT) and α-smooth muscle actin (α-SMA), in normal corneas and corneas treated with ultraviolet radiation (UVR). The wound model chosen is previously characterized, the injury is mild and the cornea heals to transparency. Methods: Rabbit corneas were exposed to UVR at the dose producing keratitis. The corneas were allowed to heal for up to 5 days and the paraffin-embedded tissue specimens were double stained and examined morphologically and immunohistochemically. Expression of CCT and α-SMA genes was investigated by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Results: There was a front of repopulating keratocytes that showed positive staining for α-SMA after 3 days. The α-SMA mRNA was already strongly expressed after 1 day, whereas the expression level of CCT was increased after 2 days. After 5 days the levels were decreased. By this time the stroma was partly repopulated by keratocytes. Conclusion: In a mild wound, the expression of α-SMA mRNA is followed by expression of mRNA of at least one subunit of the complex folding α-SMA. At protein level, α-SMA is detected in the front line of repopulating keratocytes. Expression levels for both mRNAs decline as the stroma repopulation process progresses. Copyright © Acta Ophthalmol Scand 2005.
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| 24. |
- Koulikovska, Marina, 1970-, et al.
(författare)
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Topical Biglycan Modulates Stromal Cell Apoptosis in Corneal Incisional Wound Model
- 2015
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Purpose: The purpose of this study was to determine whether exogenous topicallyapplied biglycan has an effect on corneal stromal cells during wound healing.Methods: Enzyme-linked immunosorbent assay (ELISA) was used to determine the effect of biglycan on cell survival in vitro following IL-1β induced cell death. In a corneal incisional wound model, 40 rats were wounded and treated with either topically administered biglycan or sodium chloride (sham control). At 4 hours and 1, 2, and 5 days after incision, α-smooth muscle actin (SMA) expression and apoptosis in stromal cells were evaluated by immunohistochemistry.Results: In vitro, biglycan significantly enhanced IL-1β-induced apoptosis of myofibroblasts (p = 0.038), but not corneal fibroblasts. Biglycan treated corneas exhibited reduced stromal cell apoptosis at 4 hours, day 1 and day 5 (p = 0.012, 0.040, and 0.048, respectively) and increased apoptosis at day 3 (p = 0.003) relative to controls. In wounded corneas, biglycan appeared to promote early accumulation of myofibroblasts and initiate an earlier subsequent apoptosis of these cells, relative to controls.Conclusion: Biglycan appears to accelerate corneal wound healing in vivo by modulating myofibroblast apoptosis, resulting in removal of myofibroblasts that may otherwise compromise corneal transparency.
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| 25. |
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| 26. |
- Liu, Wenguang, et al.
(författare)
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Recombinant human collagen for tissue engineered corneal substitutes
- 2008
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Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 29:9, s. 1147-1158
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Tidskriftsartikel (refereegranskat)abstract
- We successfully fabricated transparent, robust hydrogels as corneal substitutes from concentrated recombinant human type I and type III collagen solutions crosslinked with 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). White light transmission through these gels is comparable or superior to that of human corneas. Hydrogels from both type I and type III collagens supported in vitro epithelium and nerve over-growth. While both these biocompatible hydrogels have adequate tensile strength and elasticity for surgical manipulation, type III collagen hydrogels tended to be mechanically superior. Twelve-month post-implantation results of type I recombinant collagen-based corneal substitutes into mini-pigs showed retention of optical clarity, along with regeneration of corneal cells, nerves and tear film. For clinical use, implants based on fully characterized, recombinant human collagen eliminate the risk of pathogen transfer or xenogeneic immuno-responses posed by animal collagens. © 2007 Elsevier Ltd. All rights reserved.
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| 27. |
- Liu, Yuwen, et al.
(författare)
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A simple, cross-linked collagen tissue substitute for corneal implantation
- 2006
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 47:5, s. 1869-1875
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To develop a simple corneal substitute from crosslinked collagen. METHODS. Porcine type I collagen (10%, pH 5), was mixed with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The final homogenous solution was molded to corneal dimensions, cured, and then implanted into rabbits and minipigs by lamellar keratoplasty. The implants were followed for up to 6 months after surgery. Clinical examinations of the cornea included detailed slit lamp biomicroscopy, in vivo confocal microscopy, topography and esthesiometry for nerve function. Histopathologic examinations were also performed on rabbit corneas harvested after 6 months. RESULTS. Cross-linked collagen (refractive index, 1.35) had optical clarity superior to human corneas. Implanted into rabbit and porcine corneas, only 1 of 24 of the surgical corneas showed a slight haze at 6 months after surgery. All other implants showed no adverse reactions and remained optically clear. Topography showed a smooth surface and a profile similar to that of the contralateral nonsurgical eye. The implanted matrices promoted regeneration of corneal cells, tear film, and nerves. Touch sensitivity was restored, indicating some restoration of function. The corneas with implants showed no significant loss of thickness and demonstrated stable host- graft integration. CONCLUSIONS. Collagen can be adequately stabilized, using water soluble carbodiimides as protein cross-linking reagents, in the fabrication of corneal matrix substitutes for implantation. The simple cross-linking methodology would allow for easy fabrication of matrices for transplantation in centers where there is a shortage of corneas, or where there is need for temporary patches to repair perforations in emergency situations. Copyright © Association for Research in Vision and Ophthalmology.
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| 28. |
- McLaughlin, Christopher, et al.
(författare)
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Regeneration of Corneal Cells and Nerves in an Implanted Collagen Corneal Substitute
- 2008
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Ingår i: Cornea. - 0277-3740 .- 1536-4798. ; 27:5, s. 580-589
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Our objective was to evaluate promotion of tissue regeneration by extracellular matrix (ECM) mimics, by using corneal implantation as a model system.METHODS: Carbodiimide cross-linked porcine type I collagen was molded into appropriate corneal dimensions to serve as substitutes for natural corneal ECM. These were implanted into corneas of mini-pigs after removal of the host tissue, and tracked over 12 months, by clinical examination, slit-lamp biomicroscopy, in vivo confocal microscopy, topography, and esthesiometry. Histopathology and tensile strength testing were performed at the end of 12 months. Other samples were biotin labeled and implanted into mice to evaluate matrix remodeling.RESULTS: The implants promoted regeneration of corneal cells, nerves, and the tear film while retaining optical clarity. Mechanical testing data were consistent with stable, seamless host-graft integration in regenerated corneas, which were as robust as the untreated fellow corneas. Biotin conjugation is an effective method for tracking the implant within the host tissue.CONCLUSIONS: We show that a simple ECM mimetic can promote regeneration of corneal cells and nerves. Gradual turnover of matrix material as part of the natural remodeling process allowed for stable integration with host tissue and restoration of mechanical properties of the organ. The simplicity in fabrication and shown functionality shows potential for ECM
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| 29. |
- Nateghi Pettersson, Mehrdad, et al.
(författare)
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High fluence PACK-CXL as adjuvant treatment for advanced Acanthamoeba keratitis
- 2019
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Ingår i: American journal of ophthalmology case reports. - : Elsevier. - 2451-9936. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- PurposeTo describe the outcome of adjuvant high fluence photoactivated chromophore for infectious keratitis cross-linking (PACK-CXL) used to treat an advanced form of refractory Acanthamoeba keratitis (AK) diagnosed several months after initial presentation.ObservationsAn otherwise healthy 24-year old female presented with a severe unilateral keratitis. The diagnosis eluded clinicians for several months and when finally confirmed as AK, anti-amoebic therapy was instated and only appeared to be effective after addition of high fluence PACK-CXL.Conclusion and importanceIn this case of advanced AK, high fluence PACK-CXL treatment given adjuvant to pharmacologic anti-amoebic therapy resulted in lasting pain relief, re-epithelization and eradication of the Acanthamoeba parasite. Given adjuvant to anti-amoebic pharmacotherapy, high fluence PACK-CXL might be a useful method for treating typically refractory advanced AK.
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| 30. |
- Nielsen, Kim, et al.
(författare)
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Proteome profiling of corneal epithelium and identification of marker proteins for keratoconus, a pilot study
- 2006
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Ingår i: Experimental Eye Research. - : Elsevier BV. - 0014-4835 .- 1096-0007. ; 82:2, s. 201-209
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study is to identify corneal proteins differentially expressed between keratoconus and normal epithelial samples. Proteins from the corneal epithelium were isolated from 6 keratoconus and 6 myopia patients (controls) and separated by 2D-gel electrophoresis. Six % and 12% SDS-PAGE gels were used to separate low and high molecular weight proteins. Gels were silver stained and protein spots were defined by Melanie II software. The proteins that were most altered in expression comparing keratoconus and controls were extracted, trypsin-digested, and identified by mass spectroscopy. Approximately 200-500 protein spots were detected on each gel. Nineteen spots were identified as differentially expressed between keratoconus and reference epithelium including cytokeratin 3 (<7.8 fold), gelsolin (1.6 fold), S100A4 (1.9 fold), and enolase 1 (0.72 fold). Another identified protein found at very high levels was cytokeratin 12. Gelsolin, cytokeratin 3, and cytokeratin 12 have previously been described to be involved in other corneal diseases. Three proteins, gelsolin, alpha enolase, and S100A4 were identified to be differentially expressed in keratoconus compared to reference epithelium and thus may be involved in the pathogenesis. © 2005 Elsevier Ltd. All rights reserved.
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| 31. |
- Panagiotopoulos, Marios, et al.
(författare)
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Stroma remodelling during healing of corneal surface irregularities induced by PTK
- 2007
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Ingår i: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907 .- 1600-0420. ; 85:4, s. 387-394
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To study the histopathology of the remodelling process in the stroma after excimer-laser-induced corneal irregular injuries.Methods: Seven New Zealand white rabbits received in one eye a transepithelial plano photoablation (60 µm) and an additional plano ablation (25 µm). On the denuded stroma, an electron microscopy specimen grid was placed and another 25 µm ablation was applied to produce surface irregularities. Dichlorotriazinyl aminofluorescein (DTAF) was then applied for 45 seconds. Another seven right eyes of seven rabbits were ablated the same way but without using the grid, resulting in a plano ablation. All the rabbits were killed at weekly intervals after treatment. The harvested corneas from both eyes were further processed for haematoxylin-eosin staining and were also stained with monoclonal antibodies directed against Ki-67 antigen and α-smooth muscle actin (α-SMA). All specimens were examined under light and fluorescence microscope.Results: The corneal wounds were covered by epithelium during the first week. The 25 µm × 25 µm × 25 µm stromal irregularities were clearly discernible up to 3 weeks after treatment, during which time they melted and disappeared. A homogeneous zone was formed in which stroma cells laid down an initially disorganized stroma. This was sharply visible under a fluorescence microscope as a dark area between the dichlorotriazinyl aminofluorescein (DTAF) fluorescent stroma and autofluorescent epithelium. Very little response was seen in the plano-ablated wound microscopically and in terms of positive stained cells.Conclusion: As the irregularities are flattened and the homogenous zone becomes repopulated with keratocytes forming extracellular matrix material (ECM), the cornea regains its previous architecture in both groups. The irregular wound surface promotes wound-healing reactivity, a process that allows the cornea to compensate for the irregularities and heal to a functional state.
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| 32. |
- Petersson, Anders, 1967-, et al.
(författare)
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ABC om Åldersrelaterad katarakt
- 2006
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 103, s. 2393-2395
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
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| 33. |
- Podskochy, Alexander, 1971-, et al.
(författare)
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Biglycan gene expression in UVR-exposed rabbit corneas
- 2004
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Ingår i: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907 .- 1600-0420. ; 82:2, s. 200-204
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: It is known that stromal proteoglycans play an important role in the hydration and transparency of the mammalian cornea. Proteoglycans have been described as a pathological deposit in climatic proteoglycan stromal keratopathy, which is associated with chronic ultraviolet radiation (UVR) exposure. The expression of dermatan sulfate proteoglycan biglycan in the cornea was thus studied after exposure of rabbit eyes to UVR. Methods: New Zealand albino rabbit corneas were exposed to UVR at 310 nm at the dose producing biomicroscopically significant keratitis (0.47 J/cm2 ). Animals were killed 3, 7 and 28 days after exposure (five rabbits in each group). Five rabbits were used as controls and did not receive any UVR treatment. Expression of biglycan mRNA in the corneas was investigated by competitive reverse transcription-polymerase chain reaction (RT-PCR). Results: There was no expression of biglycan mRNA in the control group. In the UVR-exposed groups, biglycan mRNA had still not been expressed 3 days after exposure. The expression of biglycan mRNA was observed in all UVR-treated corneas 7 days after exposure (p < 0.05). By 28 days after UVR exposure the expression of biglycan mRNA had decreased (not statistically significant). Conclusions: There is no detectable biglycan gene expression in the normal rabbit cornea. Ultraviolet radiation exposure leads to a distinct expression of biglycan mRNA in the rabbit cornea that decreases 4 weeks after exposure, indicating the involvement of biglycan in the corneal repair process. Biglycan appears to be a novel marker of corneal wound healing.
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| 34. |
- Podskochy, Alexander, 1971-, et al.
(författare)
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Repeated UVR exposures cause keratocyte resistance to apoptosis and hyaluronan accumulation in the rabbit cornea
- 2001
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Ingår i: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907 .- 1600-0420. ; 79:6, s. 603-608
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To evaluate hyaluronan (HA) production and level of apoptosis of corneal cells after repeated UVR exposures. Methods: Fifteen albino rabbit corneas were exposed to 310 nm UVR at a dose that causes biomicroscopically significant keratitis (0.47 J/cm2). Nine rabbits received a single dose of UVR. Six rabbits were irradiated 3 times at 7-day intervals. Rabbits exposed to the single dose of UVR, were sacrificed 24 hours, 7 and 14 days after irradiation. Rabbits exposed to the repeated doses of UVR, were sacrificed 24 hours and 14 days after the last irradiation. The corneal tissue specimens were processed for histological analysis using specific staining for HA, and the TdT-dUTP terminal nick-end labeling (TUNEL) assay. Results: Corneas exposed to a single UVR dose showed extensive positive TUNEL staining 24 hours after exposure. Almost all basal epithelial cells, keratocytes throughout the entire thickness of the stroma, and endothelial cells were TUNEL-positive. No HA was found 24 hours after exposure. Extracellular HA staining of high intensity was found at day 7 throughout the entire central stroma, except the anterior one-fourth. At day 14 only a faint HA staining was detected in the posterior stroma, close to Descemet's membrane. Corneas exposed to repeated UVR doses showed at 24 hours positive TUNEL staining only in epithelial cells and in very few stromal cells. The majority of stromal cells and endothelial cells were unaffected. At the same time HA staining of very high intensity was found both at 24 hours and day 14, and it was evenly distributed throughout the entire thickness of the stroma. Conclusion: Repeated UVR exposures lead to increased production and accumulation of HA in the corneal stroma. The repopulated keratocytes are much more resistant to apoptosis than the native ones. HA accumulation may be a sign of long-term changes in the cornea.
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| 35. |
- Rafat, Mehrdad, et al.
(författare)
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PEG-stabilized carbodiimide crosslinked collagen-chitosan hydrogels for corneal tissue engineering
- 2008
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Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 29:29, s. 3960-3972
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Tidskriftsartikel (refereegranskat)abstract
- Implantable biomaterials that mimic the extracellular matrix (ECM) in key physical and physiological functions require components and microarchitectures that are carefully designed to maintain the correct balance between biofunctional and physical properties. Our goal was to develop hybrid polymer networks (HPN) that combine the bioactive features of natural materials and physical characteristics of synthetic ones to achieve synergy between the desirable mechanical properties of some components with the biological compatibility and physiological relevance of others. In this study, we developed collagen-chitosan composite hydrogels as corneal implants stabilized by either a simple carbodiimide cross-linker or a hybrid cross-linking system comprised of a long-range bi-functional cross-linker (e.g. poly(ethylene glycol) dibutyraldehyde (PEG-DBA)), and short-range amide-type cross-linkers (e.g. 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC), and N-hydroxysuccinimide (NHS)). Optimum hybrid hydrogel demonstrated significantly enhanced mechanical strength and elasticity by 100 and 20%, respectively, compared to its non-hybrid counterpart. It demonstrated excellent optical properties, optimum mechanical properties and suturability, and good permeability to glucose and albumin. It had excellent biocompatibility and when implanted into pig corneas for 12 months, allowed seamless host-graft integration with successful regeneration of host corneal epithelium, stroma, and nerves. © 2008 Elsevier Ltd. All rights reserved.
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| 36. |
- Weber, Beat A, et al.
(författare)
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Short-term impact of corticosteroids on hyaluronan and epithelial hyperplasia in the rabbit cornea after photorefractive keratectomy
- 2001
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Ingår i: Cornea. - : Ovid Technologies (Wolters Kluwer Health). - 0277-3740 .- 1536-4798. ; 20:3, s. 321-324
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. To investigate the impact of corticosteroids on subepithelial hyaluronan deposition and corneal epithelium thickness in the first 10 days after photorefractive keratectomy (PRK) and to analyze a possible contralateral effect of corticosteroids. Methods. Thirty-two New Zealand white rabbits were assigned into two groups and had a transepithelial 5.0-mm diameter, 8.00-diopter myopic PRK performed on one eye. The corticosteroid treatment group (16 animals) received 0.1 mL of methylprednisolone 4% subconjunctivally on the operation table, followed by 0.1% dexamethasone eye drops six times a day during the postoperative period. The sodium chloride (NaCl) treatment group received topical isotonic NaCl eye drops six times a day. In each treatment group, eight animals were killed after 3 and 9 days, respectively. The harvested specimens were stained for hyaluronan and the epithelial thickness was measured. Results. In contrast to the epithelial thickness, the subepithelial hyaluronan did not show a significant increase during the observation period. The corticosteroid treated group showed at both time-points significantly less subepithelial hyaluronan formation as well as a significantly thinner epithelium, when compared with the NaCl-treated group. At 9 days, the corticosteroid-treated group showed a mild epithelial hyperplasia in only one of eight eyes, whereas this was a common finding in the NaCl-treated group. We detected no hyaluronan deposits in any contralateral-untreated eye, and the epithelial thickness did not differ significantly between any of the four contralateral-untreated eye groups. Conclusions. Corticosteroid medication during the first 10 days after operation reduces the amount of subepithelial hyaluronan production and inhibits the epithelial proliferation, and epithelial hyperplasia is prevented. Neither a contralateral hyaluronan deposition nor a contralateral corticosteroid effect could be detected.
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| 37. |
- Weber, Beat A, et al.
(författare)
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Wound healing response in the presence of stromal irregularities after excimer laser treatment
- 2001
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Ingår i: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907 .- 1600-0420. ; 79:4, s. 381-388
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To trace the fate of stromal irregularities after excimer laser treatment and to increase our knowledge of the reasons why surface irregularities in the ablation bed cause inferior postoperative results. Methods: Twelve New Zealand White rabbits received a transepithelial photoablation to a preset depth of 60 ╡m. An electron microscopy specimen grid was then placed on the denuded stroma and another 20 ╡m ablation was applied in order to produce surface irregularities. Another six rabbits received a plano transepithelial photoablation to a preset depth of 80 ╡m. The treated corneas were harvested at various timepoints and differentially further processed for microradiography, hematoxylin-eosin-, hyaluronan (HA)- and leukocyte protein L1 staining. Results: In the grid treated corneas the subepithelial mesh pattern is clearly discernible after 1 week, and after 4 weeks it is replaced by a subepithelial layer containing HA and water. The thinning of this layer between 1 and 12 weeks is statistically significant (p<0.05). After 4 and 8 week the plano treated corneas only exhibit some subepithelial HA- and water accumulation. After 1 day the grid treated corneas show an extensive stromal infiltration of leukocytes. In the plano treated corneas the leukocytes mainly remain on the surface. Conclusions: During the healing process stromal irregularities are flattened, leaving a homogeneous zone with increased water content. This subepithelial layer is rarefying as new subepithelial tissue is forming. Postablational irregularities induce a more pronounced healing reaction when compared to a smooth ablation surface. Leukocyte infiltration seems to play a role in this process.
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| 38. |
- Xeroudaki, Maria, 1989-
(författare)
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Advanced surgeries, medicines and materials for corneal regeneration
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Corneal transplantation is often the only treatment option in cases of corneal blindness, with the main challenges being the scarcity of human donors, risk for graft failure and suboptimal visual outcome due to suture-related issues. Alternative therapies are sought that either address the above transplantation issues directly or stimulate the cornea’s repair mechanism and regenerative properties to restore transparency without the need for transplantation. The first aim of this thesis was to develop a cell-free substitute for the human corneal stroma made of porcine collagen, a purified byproduct from the food industry that is already approved by FDA as a raw material, used for example in cosmetic surgery or as a medical device in glaucoma surgery. Abundance, cost-effectiveness, low rejection risk due to acellularity, high purity and worldwide availability are among the main advantages of purified porcine collagen compared to human donors and other corneal stromal substitutes. The second aim was to address the risk of graft rejection in cases of neovascularized and inflamed corneas by loading the bioengineered porcine collagen constructs with drugs that can ideally promote corneal regeneration, secure the survival of the graft in cases of high-risk keratoplasties and minimize the need for prolonged topical immunosuppressive therapy following operation, which has drawbacks of low bioavailability and need for good patient compliance. The third aim was to develop alternative techniques of lamellar transplantation, all assisted by femtosecond laser, that are less suture-dependent and enable the intrastromal implantation of biomaterials. Finally, the fourth aim of this thesis was to evaluate the role of Regenerating Agent (RGTA) eye drops in corneal wound healing following therapeutic laser ablation of the cornea in a randomised, blinded, placebo-controlled preclinical study. Regenerating Agent is a biomimetic of extracellular matrix with well-established favourable outcomes in the treatment of skin wounds and preliminary positive results in the treatment of corneal wounds. Different manufacturing protocols were used to enhance the mechanical properties of bioengineered porcine collagen (BPC) and to address different requirements. The combination of both chemical and photochemical crosslinking with riboflavin and ultraviolet A light (to form BPCDX) and reinforcement with cellulose nanofibers extracted from the Ciona intestinalis sea invertebrate (BPCDX-CNF) resulted in stronger biomaterials compared to earlier BPC versions. The biomaterials could be manufactured in different sizes and in core-and-skirt forms with the peripheral skirt degrading faster due to mechanical compression without the addition of any cross-linkers during manufacturing. BPC could be successfully loaded with nerve growth factor (NGF) and BPCDX-CNF with dexamethasone without sacrificing transparency and both drugs could be released from BPC-based materials in vitro up to at least 2 months. The biological activity of dexamethasone released from the drug-loaded BPCDX-CNF could be confirmed by the decreased expression of inflammatory cytokines in human corneal epithelial cells grown on dexamethasone-loaded BPCDX-CNF. A compatible packaging and sterilization process was developed for BPCDX, tested internally and externally by Good Laboratory Practice-certified laboratories, that can enable worldwide distribution and storage at room temperature or in a refrigerator up to two years without the need of extra quality controls before transplantation. BPC-based materials could be safely implanted in rabbit, minipig and human corneas with advanced keratoconus using femtosecond-laser assisted intrastromal keratoplasty procedures. A femtosecond laser was used to create intrastromal pockets of different dimensions based on the size of the biomaterials. Through an access cut or by lifting a flap, both created by femtosecond laser, biomaterials could be implanted intrastromally with or without native tissue removal. Additional sutures were used in a surgical inflammatory model to test the biological activity of dexamethasone released by BPCDX-CNF. These minimally invasive surgical procedures required shorter period of immunosuppression following operation and maintained the anatomy of the surrounding host tissue. Apart from the skirt part of the composite BPC that was mechanically compressed and was designed to degrade faster, the crosslinked BPC remained stable in animal models, while no degradation was observed in the BPCDX 2 years after implantation in humans. The biomaterials were biocompatible and native cells were found in the biomaterial-host interface or in the periphery of the biomaterial. The inflammatory response following operation depended on individual response to injury and did not appear to be stimulated by BPC implantation. Neovascularization and haze formation were mainly restricted around the sutures used to secure either the access cut or flap overlying the biomaterials as well as intentionally placed close to the limbus to trigger inflammation in the dexamethasone study. In the human studies, no sutures were used and corneal transparency was maintained at the highest level in all subjects after 2 years without any signs of rejection, inflammation, vascularization or scarring. Topographic indices including mean anterior corneal curvature and maximal corneal apical curvature were significantly reduced in both clinical cohorts resulting in improved best corrected visual acuity. Importantly, following operation all human subjects could tolerate contact lenses and no subject was considered legally blind. The release of dexamethasone from the drug-loaded BPCDX-CNF could be also confirmed in vivo by sustained intraocular pressure increase, tendency to reduce neovascularization and haze formation and sustained suppression of inflammatory cytokines in the aqueous humor of eyes implanted with dexamethasone-loaded BPCDX-CNF compared to non-loaded BPCDX-CNF. Finally, RGTA eye drops following excimer laser ablation of the anterior healthy rabbit cornea did not affect the already quick and uneventful epithelial closure. Although there was significantly less haze in the RGTA group compared to placebo as measured by in vivo confocal microscopy, this decrease was not clinically relevant as all corneas in both groups were clinically transparent following laser. The microscopic haze formation and staining problems did not allow quantification of nerve regeneration, but subbasal nerves were found to repopulate the central ablated regions in both RGTA and placebo groups. In conclusion, our results indicate that biomaterials made of bioengineered porcine collagen are a safe alternative to human donor tissue for corneal transplantation, offering the advantage of custom-made manufacturing to address different requirements with potential applications to different corneal stromal diseases. Femtosecond laser enables safe intrastromal implantation of biomaterials with less suture-related issues and immunosuppression following operation compared to traditional corneal transplantation methods. Regenerating Agent eye drops do not affect the already rapid wound healing following laser ablation of the healthy cornea.
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