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| January 2008 | Inside IOVS | Volume 49/1 |
Connexin43 Knockdown: A New Therapeutic Approach for Corneal Endothelial Injury
The corneal endothelium is extremely vulnerable to injury because it lacks a robust proliferative response after injury and undergoes endothelial-mesenchymal transition/transformation (EMT) leading to corneal fibrosis and eventual loss of visual acuity. An appropriate treatment for corneal endothelial injury that circumvents the lack of proliferative response and inhibits EMT has yet to be developed. Nakano et al. (p. 93) explored a gap junction protein connexin43 (Cx43) knockdown approach as an efficient wound treatment using an in vivo rat model of scrape injury to the corneal endothelium. They demonstrated that Cx43 knockdown accelerates wound closure but inhibits EMT, suggesting that Cx43 knockdown might be a new therapeutic approach not only for acceleration of wound healing but also for prevention of tissue fibrosis by inhibiting EMT.
Amniotic Membrane Transplantation for Healing of Bacterial Keratitis
Amniotic membrane (AM) is used for many ocular surface disorders. Barequet et al. (p. 163) studied the efficacy of AM transplantation as an adjunctive treatment in corneal healing after experimental Staphylococcus aureus keratitis in rats' eyes. Eyes treated with cefazolin and AM transplantation had clinically less corneal haze and neovascularization, and histopathologically smaller and less congested central corneal vessels, as compared to eyes treated with either cefazolin drops without AM transplantation and eyes treated with saline and AM transplantation. These findings suggest that AM transplantation can be a useful adjunctive treatment for improving the healing of the cornea after bacterial keratitis.
Mucin O-Glycans Prevent Apical Adhesion in Corneal Epithelial Cells
Cell surface-associated mucins expressed by the human ocular surface epithelia are composed of up to 55% carbohydrates, or O-glycans. Sumiyoshi et al. (p. 197) have used static and dynamic flow adhesion assays in corneal epithelial cells to demonstrate that O-glycans have an anti-adhesive character at the apical cell surface. Their findings suggest that O-glycans contribute to preventing the tarsal conjunctival epithelial surfaces of the eye from adhering to the cornea during blinking or sleeping. Alteration in the distribution of mucin O-glycans, which has been demonstrated in patients with dry eye, may result in adherence and damage to the epithelial surface by abrasive stress.
Iron Regulates L-Cystine Uptake and GSH Levels by Its Effect on C-Aconitase
Iron is necessary for many essential functions; however, in excess it has the capacity to generate reactive oxygen species. Lall et al. (p. 310) provide evidence that iron regulates L-glutamate secretion, L-cystine uptake and the downstream production of the powerful antioxidant glutathione (GSH) by way of a cytosolic aconitase in lens epithelial and retinal pigment epithelial cells. Therefore, one of iron’s critical roles may be that it participates in cellular defense against its own potential oxidative damage. Since c-aconitase is present in all mammalian cells so far studied, it is likely to be a universal pathway.
Decrease in Choroidal Circulation Occurs before Formation of Choroidal Neovascularization in AMD
Metelitsina et al. (p. 358) observed lower foveolar choroidal blood flow parameters at baseline in eyes of patients with age-related macular degeneration (AMD) who later developed choroidal neovascularization (CNV) than in eyes of patients that did not develop CNV over the study follow-up. Eyes with lower choroidal blood flow at baseline were also more likely to develop visual loss. In addition, decreases in choroidal blood flow were identified prior to CNV formation. These findings suggest that decreases in the foveolar choroidal circulation, and possibly frank ischemia, may play a role in CNV development.
CNTF Maintains Retinal Sensitivity to Electrical Stimulation in RCS Rats
As photoreceptors are lost in retinal degenerative diseases, the amount of electrical current required to elicit responses increases. Kent et al. (p. 372) found that ciliary neurotrophic factor (CNTF), chronically infused into the vitreous of RCS rats, resulted in a dose-dependent maintenance of retinal sensitivity to electrical stimulation. These findings suggest that pharmacological methods for retinal neuroprotection may enhance the function and long-term viability of retinal prosthetic devices.
Increased Intraretinal PO2 after Photocoagulation
Indirect evidence suggests that panretinal photocoagulation (PRP) is successful in treating diabetic retinopathy because it destroys photoreceptors and increases inner retinal PO2. Increased PO2 has not generally been demonstrated with preretinal vitreous PO2 measurements, however. Budzynski et al. (p. 380) made oxygen recordings in air-breathing cats after retinal photocoagulation. Intraretinal PO2 increased significantly, although preretinal PO2 did not. The increase also occurred after occlusion of the retinal circulation, similar to the capillary loss in diabetic retinopathy. Intraretinal PO2 increased even though choroidal PO2, which provides the source of increased oxygenation, decreased. This work supports the hypothesis that increased intraretinal PO2 is important in the mechanism of PRP.
Induction of Functional Photoreceptor Phenotype in Retinal Stem Cells
Retinal stem cells (RSCs) from the ocular ciliary marginal zone have the potential to be directed into specific, functional photoreceptor phenotypes, as the study of Jomary and Jones (p. 429) using exogenously-provided Crx expression shows. This finding lends support to the notion that specific retinal cell types can be generated from RSCs by genetic modification and opens the prospect of producing functional replacement cells with therapeutic capabilities for the treatment of a range of retinal diseases.
The Defensin DEFB-109: A Novel Role at the Ocular Surface?
Abedin et al. (p. 28) used conventional and real-time polymerase chain reactions to profile the constitutive expression of the b-defensin DEFB-109 on ocular surface epithelial cell samples and its remarkable downregulation in inflammatory and infective states. These results contradict assumptions of direct antimicrobial activity and point to novel actions and interactions at this important mucosal surface. These initial findings raise questions about microbe-host interaction and may hold the key to the discovery of an alternative role of peptides such as DEFB-109 on the ocular surface.
Heritability of Optic Disc, Cup, and Rim Areas
Healey et al. (p. 77) have carried out a classical twin study, looking at the heritability of optic disc parameters, namely the optic disc, optic disc cup, and optic disc rim areas. Genetic factors were found to explain 73%, 66%, and 34% of the variation in these area measurements, respectively. These findings may help to further elucidate the understanding of the mechanisms of glaucoma and the susceptibility of the optic disc to this disorder. Greater understanding about mechanisms may also help to identify disease-modifying agents or environmental interventions to reduce disease in susceptible individuals.
Intramuscular Growth Factor Injection: A Non-surgical Treatment for Strabismus?
Future pharmacological treatment of strabismus may be optimized if drugs less potentially toxic to patients can be developed. Anderson et al. (p. 221) examined the physiological and morphometric effects of direct EOM injection with growth factors BMP4, TGFb1, Shh or Wnt3A. One week after a single injection of any of these factors, treated muscles showed significant decreases in both force generation and mean cross-sectional area of fast MyHC-positive myofibers when compared to control muscles. These results suggest that, rather than using toxins or immunotoxins, a more biological approach to decreasing muscle strength is possible and demonstrate the potential utility of myogenic signaling factors for decreasing EOM strength. Ongoing drug-delivery studies will elucidate means of extending treatment effect to make such agents clinically useful.
Photoreceptor Progenitor Cells Are Produced in the Pars Plana
Nishiguchi et al. (p. 422) report that a part of the neuroblast layer, a layer known to be composed of retinal progenitor cells, actually resides within the ciliary epithelium of the pars plana during post-natal ocular development in mice. Moreover, cone and rod photoreceptor precursors in various stages of morphological development are identified in the pars plana not only during development but also after retinal injury even in adult animals. These results indicate that photoreceptor precursors are produced in the pars plana and that they may serve as a potential source for photoreceptor replacement therapy.
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