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| January 2004 | Inside IOVS | Volume 45/1 |
Catalase and PRDX5 Protection of Alcohol-Induced Eye Defects
Up to 90% of children with prenatal alcohol exposure may show varying degree of eye abnormalities. Peng et al. (p. 23) demonstrate that overexpression of catalase and peroxiredoxin 5 (PRDX5) provide significant protection against alcohol-induced eye defects in Xenopus embryos. The protective actions of these enzymes are mediated by restoration of the alcohol-sensitive eye markers including Pax6, VAX2, and TBX5. Therefore, combined antioxidative and antinitrosative therapy may potentially become an effective method to prevent eye anomalies and other developmental defects in embryos exposed to alcohol.
Cre-recombinase Transgenic Mouse Strains
Conditional gene targeting using Cre/loxP system is a powerful approach to investigate gene function in a specific cell-type and/or at a particular developmental stage. An important component for this strategy is the availability of transgenic mice expressing Cre-recombinase in a cell-type restricted manner. The report of Akimoto et al. (p. 42) describes the generation of lines of transgenic mice that express Cre-recombinase under the control of M- or S-opsin promoter, and hence in M- or S-cones, respectively. These transgenic strains will be useful for producing conditional mouse mutants to investigate the function of genes in cone photoreceptors, opening new avenues in cone biology.
NeuroD Specifies a Photoreceptor Fate
Identifying "decision making" genes that determine a photoreceptor cell's fate bears clinical implications as the gene may be employed to guide stem cells to differentiate into photoreceptors for cell replacement therapies. Yan and Wang (p. 48) performed loss-of-function analyses and showed that neuroD, a bHLH gene, is required for photoreceptor formation during retinal development. Previously, through gain-of-function studies, they demonstrated that neuroD alone is sufficient to guide retinal cells or cultured RPE cells to differentiate/transdifferentiate along the photoreceptor pathway. Their studies indicate that neuroD may be one of the critical genes that determines the photoreceptor cell's fate.
Vitreous Body Liquefaction and Nuclear Cataracts
Destruction of the vitreous gel by vitrectomy or other factors (Stickler syndrome, high myopia) has been associated with nuclear cataract formation. The vitreous body also degenerates to a variable extent in older persons. In a study of eye bank eyes, Harocopos et al. (p. 77) found that the extent of vitreous liquefaction strongly associated with nuclear, but not cortical or posterior subcapsular opacities, independent of age. The authors suggest that the vitreous gel protects the lens from oxygen from the retina. Protecting or restoring the vitreous gel may prevent or delay this type of cataract.
A Possible Mechanistic Role for TGF-β2 in Primary Open-Angle Glaucoma
It has been known for some time that levels of TGF-β2 are elevated in the aqueous humor of patients with primary open-angle glaucoma, but the functional significance of this finding has been unclear. Gottanka et al. (p. 153) report on experiments using cultured human anterior segments that show that sustained levels of TGF-β2 reduce outflow facility, lead to accumulation of extracellular material within the juxtacanalicular tissue and reduce the size of Schlemm's canal. These findings point to TGF-β2 as a contributory factor in inducing ocular hypertension, presumably by its influence on extracellular matrix in the trabecular meshwork.
Pressure and Drug Responsiveness of the Rat Ophthalmic Artery
In this study the authors quantified the pharmacological responses and the response to intravascular pressure in intact pressurized ophthalmic arteries of the rat. Jarajapu et al. (p. 253) show a robust myogenic tone response in this artery that developed at low pressure and was maintained up to 200 mmHg. Myogenic tone protects the retinal vasculature from systemic pressures that may be experienced in vivo. Impaired myogenic tone is associated with systemic diseases such as hypertension and diabetes as are changes in pharmacological responsiveness. This study forms the basis of further pharmacological and (patho)physiological mapping of the changes associated with diabetic eye disease.
Experimental subRPE Deposit Formation in the APO B100 Mouse
Dietary intake of polyunsaturated fats has been associated with the dry form of age-related macular degeneration. Various animal models have also shown the accumulation of various deposits after ingestion of high fat diet. In this issue, Espinosa-Heidmann et al. (p. 260) report that young APO B100 transgenic mice develop basal laminar deposits beneath the RPE after a high fat diet, but require exposure to blue light in order to initiate the process. The mice developed hyperlipidemia, but did not demonstrate neutral lipid or cholesterol deposition in the deposits or in Bruch’s membrane. Vitamin E pre-treatment prevented deposit formation. This study demonstrates that a high fat diet is necessary to induce deposits, but deposit formation involves complex interaction between plasma lipidemia, ocular oxidant exposure and anti-oxidant protection.
Subretinal Transplantation of Engineered Schwann Cells
Recent publications have shown that retinal grafts of primary Schwann cells (derived from sciatic nerve) can limit photoreceptor loss in the dystrophic RCS rat and the rhodopsin knock-out mouse, probably because of the release of beneficial growth factors. Lawrence et al. (p. 267) have expanded this work using Schwann cell lines engineered to overproduce either BDNF or GDNF as donor cells. Both cell lines maintained photoreceptor numbers and visual function in the dystrophic RCS rat, but, in the experimental conditions described, the retinas that received grafts of cells overproducing GDNF demonstrated greater functional and anatomical preservation.
RPE Resists Immune T Cell Destruction
Transplantation of foreign retinal pigment epithelial (RPE) cells into the subretinal space may be a promising future way to treat retinal diseases such as macular degeneration. It is important to know whether these cells are vulnerable to immune rejection at this site. Zamiri et al. (p. 177) have demonstrated both in vivo and in vitro that RPE are highly resistant to destruction by immune T cells. These results, which mirror the immune privileged status of RPE tissue as a graft, imply that immune barriers to acceptance of foreign RPE grafts may be low compared to non-ocular tissues. This augurs well for the future success of RPE transplantation as therapy.
An Episcleral, Retrobulbar Ocular Drug Delivery System
Many macular diseases require a long-term drug therapy to supply effective doses to the posterior pole of the eye. Kato et al. (p. 238) designed an episcleral implant which was placed retrobulbarly and delivered betamethasone transsclerally to the posterior pole of the eye, and evaluated the intraocular pharmacokinetics after implantation and its safety. Concentrations of the drug in the retina-choroid were maintained above the concentrations effective for suppressing inflammation for at least 4 weeks without any toxic reactions. These findings suggest that this implant may be a useful drug carrier especially for the posterior pole of the eye.
Novel Growth Promoting Factor for RPE Cells
RPE cells play critical roles in maintaining the homeostasis of the retina and in controlling choroidal neovascularization. Because the denaturation of cellular proteins in the RPE or the loss of function of RPE cells are responsible for retinal and choroidal diseases, a factor that stimulates RPE cell growth could prove to be valuable for the treatment of RPE-related ocular diseases. Tanaka et al. (p. 245) have isolated a 31kDa factor with growth promoting activity for RPE cells and named it REF-1. The amino-terminal sequence was determined, and molecular cloning of its cDNA showed that the factor was identical to tissue-factor pathway inhibitor-2.
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