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- 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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| 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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| 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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| 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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| 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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| 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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| 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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| 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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