Macular Degeneration: Xu Q

Bora NS, Kaliappan S, Jha P, Xu Q, Sivasankar B, Harris CL, Morgan BP, Bora PS. · Department of Ophthalmology, Jones Eye Institute, Pat and Willard Walker Eye Research Center, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. · J Immunol. · Pubmed #17237428 links to  free full text

Abstract: We have shown that membrane attack complex (MAC) formation via the activation of the alternative pathway plays a central role in the laser-induced choroidal neovascularization (CNV). This study was undertaken to understand the role of a complement regulatory protein, CD59, which controls MAC assembly and function, in this model. CNV was induced by laser photocoagulation in C57BL/6 and Cd59a(-/-) mice using an argon laser. Animals from each group were sacrificed on day 1, 3, 5, and 7 postlaser. Retinal pigment epithelium-choroid-scleral tissue was examined to determine the incidence and size of CNV complex, and semiquantitative RT-PCR and Western blot analysis for CD59a was studied. Recombinant soluble mouse CD59a-IgG2a fusion (rsCD59a-Fc) protein was injected via i.p. or intravitreal routes 24 h before laser. Our results demonstrated that CD59a (both mRNA and protein) was down-regulated during laser-induced CNV. Cd59a(-/-) mice developed CNV complex early in the disease process. Increased MAC deposition was also observed in these Cd59a(-/-) mice. Administration of rsCD59a-Fc inhibited the development of CNV complex in the mouse model by blocking MAC formation and also inhibited expression of angiogenic growth factors. These data provide strong evidence that CD59a plays a crucial role in regulating complement activation and MAC formation essential for the release of growth factors that drive the development of laser-induced CNV in mice. Thus, our results suggest that the inhibition of complement by soluble CD59 may provide a novel therapeutic alternative to current treatment.

Bora PS, Kaliappan S, Xu Q, Kumar S, Wang Y, Kaplan HJ, Bora NS. · Department of Ophthalmology and Visual Science, Kentucky Lions Eye Center, University of Louisville, KY, USA. · FEBS J. · Pubmed #16689928 No free full text.

Abstract: One of the pathologic complications of exudative (i.e. wet-type) age-related macular degeneration (AMD) is choroidal neovascularization (CNV). The aim of this study was to investigate whether chronic and heavy alcohol consumption influenced the development of CNV in a rat model. The oxidative metabolism of alcohol is minimal or absent in the eye, so that ethanol is metabolized via a nonoxidative pathway to form fatty acid ethyl esters (FAEE). Fatty acid ethyl ester synthase (FAEES) was purified from the choroid of Brown Norway (BN) rats. The purified protein was 60 kDa in size and the antibody raised against this protein showed a single band on western blot. BN rats on a regular diet were fed alcohol for 10 weeks. Control rats were fed water with a regular diet and pair-fed control rats were fed regular diet, water and glucose. We found that FAEES activity was increased 4.0-fold in the choroid of alcohol-treated rats compared with controls. The amount of ethyl esters produced in the choroid of 10 week alcohol-fed rats was 7.4-fold more than rats fed alcohol for 1 week. The increased accumulation of ethyl esters was associated with a 3.0-fold increased expression of cyclin E and cyclin E/CDK2; however, the level of the cyclin kinase inhibitor, p27Kip, did not change. The increased accumulation of ethyl esters was also associated with 3.0-fold decreased expression of APN in the choroid. We also found that the size of CNV increased by 28% in alcohol-fed rats. Thus, our study showed that chronic, heavy alcohol intake was associated with both an increased accumulation of ethyl esters in the choroid and an exacerbation of the CNV induced by laser treatment. These results may provide insight into the link between heavy alcohol consumption and exudative AMD.

Wang F, Wang H, Zhuang J, Xu Q. · Department of Ophthalmology, Shanghai Shibei Hospital, Shanghai 200435, China. · Yan Ke Xue Bao. · Pubmed #12579676 No free full text.

Abstract: PURPOSE: To explore the image features of exudative age-related macular degeneration (AMD) with B-scan. METHODS: Using NIDEK US-3300 model B-scan to observe 31 patients (54 eyes) with AMD. RESULTS: The membranous arc echo was found at the posterior polar and there was a shuttle absence of echo between the echo band and the wall of eyeball in the period of retinal pigment epithelium detachment. During the exudation and hemorrhage absorbed not comletely, mixed echo was seen. A small parenchyma body with protrusion was seen with stronger echo in the late phase when the exudation and hemorrhage were replaced by the scar tissues, it was like a convex lens or a triangle and the top pointed to the globe behind, but it was flat towards the vitreous. CONCLUSION: The B-scan examination is valuable in diagnosis, treatment and follow-up for exudative AMD.