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| November 2002 | Inside IOVS | Volume 43/11 |
| Promoting Ocular Cell Health and Viability |
TFF-Peptides and Tear Outflow
TFF-peptides promote migration of epithelial cells in vitro, they have anti-apoptotic properties, they induce cell scattering, and they influence the rheological properties of the tear film. In the present study, Paulsen et al. (p. 3359) demonstrate that TFF3 and, in some cases, TFF1 are synthesized by the epithelium of the efferent tear ducts suggesting that both peptides ease tear flow through the efferent tear ducts and may also influence epithelial healing due to their motogenic properties. Moreover, the results reveal nuclear TFF3 staining in single sections which was not inhibited with a corresponding synthetic peptide pointing to the presumption that nuclear staining of TFF3 seems to be artificial.
Hydrogels and Cytoprotection
Debbasch et al. (p. 3409) explore cell toxicity and anti-oxidant effects of preserved and unpreserved hyaluronic acid and carbomer 934P by using an in vitro model of Chang conjunctiva. This study demonstrates that two major ophthalmic hydrogels (unpreserved and preserved) have no cytotoxicity but anti-oxidant properties and tend to reduce the toxic effects of benzalkonium chloride. It should be interesting in the future to use low concentrations of hydrogels in association with ophthalmic drugs in order to improve ocular tolerance.
UV Light, Cytokines, and Pterygia
While the pathogenesis of pterygia remains a mystery, epidemiological evidence supports a role for environmental stress such as UV light in pterygium formation. Di Girolamo et al. (p. 3430) have demonstrated the induction of inflammatory and angiogenic cytokines in both pterygium tissue and cultured pterygium epithelial cells following UVB exposure. It is likely that these cytokines sustain the invasive growth characteristics of this lesion. While targeting such cytokines may be of therapeutic benefit, strategies aimed at reducing ocular exposure to UV may be the best form of disease prevention.
Gene Therapy and Retinal Detachment
Photoreceptors protection may be a crucial step for functional restoration after surgeries in retinal detachment. Wu et al. (p. 3480) have shown that the gene of glial cell line-derived neurotrophic factor (GDNF), carried by viral vectors, can be expressed in large amounts in photoreceptors. GDNF protects photoreceptors from apoptosis after retinal detachment and suppresses subretinal proliferation by Müller cells. This study suggests that gene therapy could be a good adjunct to present surgeries.
Bucillamine in CNV
Development of a pharmacological therapy for choroidal neovascularization (CNV) is long overdue. To achieve this goal, it would be helpful if a drug already approved for clinical use could suppress CNV. Yanagi et al. (p. 3495) tested whether bucillamine, a disease-modifying anti-rheumatic drug that has been in clinical use for more than ten years, could suppress an experimental model of CNV induced by photocoagulation in pigmented rats. Consequently, the authors found that subconjunctival infection of bucillamine reduced the leakage and size in CNV. Their findings suggest bucillamine may be beneficial in treating CNV.
DNA Repair in Photoreceptor Degeneration
Bright light triggers photoreceptor DNA strand breaks and apoptotic cell death. Several factors, including antioxidants, inhibition of photoreversal, preservation of the mitochondrial membrane potential (DYm), and prevention of enzyme activation, reduce the degree of damage. Many investigators elicit neuroprotection by blockade of enzymes of the apoptotic pathway. The present study by Gordon et al. (p. 3511) suggests an alternative neuroprotective strategy: DNA repair. The authors’ results raise the possibility that maintenance of in-house DNA repair can provide rescue of photoreceptors during stress-induced damage. Moreover, DNA-repair mechanisms may provide a useful drug target to promote photoreceptor survival in retinal degenerations.
Zeaxanthin Protects Photoreceptors
Indirect evidence indicates that higher concentrations of macular pigment carotenoids - lutein and zeaxanthin - may reduce risk for age-related macular degeneration (AMD). Thomson et al. (p. 3538) used a quail model to test the hypothesis that zeaxanthin protects photoreceptors from damage by intermittent white light. The number of apoptotic rods and/or cones was very significantly and negatively correlated with the concentration of zeaxanthin in the retina, but not in the serum. These data provide the first experimental evidence that a retinal carotenoid protects photoreceptors, and suggest that elevating macular pigment could be beneficial in AMD.
A P2Y2 Receptor Agonist and Retinal Edema
Subretinal or intra-retinal accumulation of fluid is a major cause of visual loss in a variety of retinal disorders, including retinal detachment, exudative AMD, and diabetic and cystoid macular edema. Robust pharmacological stimulation of subretinal fluid reabsorption may be therapeutically useful to help restore vision or stem further visual loss in these diseases. Two separate studies by Maminishkis et al. (p. 3555) and Meyer et al. (p. 3567) now show that a synthetic, hydrolysis-resistant P2Y2 receptor agonist, INS37217, stimulates fluid absorption across freshly isolated RPE and enhances subretinal fluid reabsorption in rat and rabbit models of retinal detachment. These results support the development of INS37217 for treating retinal detachment and edema.
aB-Crystallin Inhibits RPE Apoptosis
Apoptosis of retinal pigment epithelial cells (RPE) is considered to be a crucial event in the pathogenesis of age-related macular degeneration (AMD). Many stress stimuli capable of triggering apoptosis induce the synthesis of heat shock proteins (HSP) that confer a cytoprotective effect. The study of Alge et al. (p. 3575) provides evidence for oxidative stress-induced caspase-3 activation and aB-crystallin induction in human RPE and demonstrates that overexpression of aB-crystallin reduces caspase-3 activity and cell death in RPE cells. aB-crystallin might therefore function as a stress-inducible antiapoptotic HSP in human RPE and overexpression may provide a mechanism to postpone cell death in response to cellular stress.
Interfering with Retinal Cell Death
Retinal degenerations may be viewed as disorders involving two distinct phases: an initial malfunction at the genetic/biochemical level followed by a wave of apoptotic cell death. As reported in Tuohy et al. (p. 3583), studies with a retinal cell culture, 661W, provides an opportunity to test strategies directed towards interfering with the later phase. Inhibiting cell death may provide therapeutic benefit on its own in addition to stabilizing a dwindling cell population. Once stabilized it may then be possible to address the introduction of additional therapeutic strategies directed at the primary phase of the disorder.
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