Diseases of the Retinal Pigment Epithelium-Photoreceptor Complex in Nonrodent Animal Models

Book Overview: The retinal pigment epithelium is a critical tissue within the eye. It lies directly behind the retina, where it provides metabolic support to the photoreceptors and controls their local environment. As a result, the RPE is vital to retinal function, but also a site of aging and disease that cause dysfunction and visual loss. This book brings together comprehensive reviews of basic and clinical science concerning the RPE. It is organized to juxtapose chapters on RPE disease with chapters on the underlying pathophysiology. These include up-to-date accounts of growth factors, laser effects, proliferative vitreoretinopathy, Bruch\u27s membrane pathology, as well as new diagnostic tools such as ocular coherence tomography, in vivo imaging of lipofuscin and non-photic electrical responses. Other chapters cover pharmacology and toxicology, mechanisms of retinal adhesion and detachment, RPE pigments and transport, congenital and dystrophic diseases, animal models of RPE disease, and different aspects of age-related macular degeneration. The history and evolutionary aspects of the RPE are also presented. The contributing authors are experienced clinicians and eminent basic scientists who work on this critical part of the eye. The book will be a valuable resource for anyone interested in the eye, and a necessity for specialists in the fields of retinal physiology and retinal disease

Posterior Segment Approach for Subretinal Transplantation or Injection in the Canine Model

A posterior segment approach for cell transplantation or injection into the subretinal space of the dog has been developed. Controlled penetration to the subretinal space was achieved using a 29-gauge injection cannula, either blunted or with a 30° sharpened bevel, and partially ensheathed with moveable plastic tubing. Depending on the injection volume used, the retina detached, and the fluid was reabsorbed within 1–3 weeks, although for smaller volumes the retina reattached within a matter of days. The optimal injection volume used was between 100 and 150 μl, or two injections of 55 μl each. By ophthalmoscopy following the surgery, it was possible to serially monitor the injection site and retinal bleb through fundus photography. Light microscopy demonstrates the distribution of stable, viable RPE cells in the subretinal space up to 6 months. The transplantation technique developed for the dog is atraumatic and free from any major surgical or clinical complications. It can be readily used to deliver cells or fluids to localized regions of the subretinal space

Expression of a secreted fibroblast growth factor binding protein-1 (FGFBP1) in angioproliferative Kaposi sarcoma

Objective: Kaposi’s sarcoma (KS) is an angioproliferative disease frequently seen in patients with the acquired immunodeficiency syndrome (AIDS). Previous studies suggest that the HIV-1 protein Tat and Fibroblast Growth Factor 2 (FGF-2) have synergistic angiogenic effects in AIDS-KS tumors. However, the mechanisms by which FGF-2 is released and activated in KS tumors are not clearly defined. We carried out this study to determine whether an FGFbinding protein (FGFBP1 or BP1) that enhances the angiogenic activity of FGF-2 is expressed in AIDS-KS tumors, and to define whether BP1, FGF-2, and HIV-Tat protein-protein interactions could play a potential clinically role in the pathogenesis of AIDS-KS. Methods: BP1 was localized in AIDS-KS lesions by immunohistochemistry and in situ hybridization studies. The binding of radiolabeled FGF-2 to His-tagged BP1 or the FGF-receptor 1 was assessed in the presence and absence of HIV-Tat and other viral proteins. Mice carrying tetracycline-regulated BP1 transgene mice were used to determine whether activation of BP1 during wound healing induces KS-like lesions. Results: BP1 expression was detected in AIDS-KS tumor keratinocytes, spindle cells, and infiltrating mononuclear cells. In addition, HIV-Tat competed for the binding of FGF-2 to immobilized BP1, but does not affect the interactions of FGF-2 with its high affinity receptor (FGFR-1). In contrast, two other HIV-proteins, Nef and gp120, did not affect the binding of FGF-2 to BP1 or to FGFR-1. Finally, up-regulation of BP1 expression in tetracycline-regulated –conditional BP1 transgenic mice subjected to skin wounds, induced KS-like skin lesions. Conclusion: Taking into consideration the results of previous studies showing that both HIV-Tat and BP1 enhance the mitogenic and angiogenic activity of locally-stored FGF-2, both in vitro and in vivo, our findings suggest a novel mechanism by which the release and activity of FGFs can be modulated in AIDS-KS tumors by HIV-Tat as well as BP1

Genome-wide analysis identifies common CNVs associated with primary open angle glaucoma

BackgroundCopy number variation (CNV) is one of the major factors contributing to genomic diversity and diseases. Glaucoma is a major neurodegenerative disease causing irreversible vision loss across the globe. We wanted to analyze the impact of common CNVs in a genome-wide scale in patients of primary open angle glaucoma (POAG) collected from the West Bengal, India.MethodGenome-wide data was generated on 364 POAG cases and 365 controls on Illumina 660W-Quad arrays and CNVs were called using PennCNV. Copy number variant regions (CNVRs) were analyzed for association. A publicly available dataset of POAG cohort of 866 cases and 495 controls from Caucasian origin (GLAUGEN study) was used as a validation cohort. Representative CNVs were validated using real-time PCR.ResultsWe analyzed genome-wide CNV from 1928 samples. After association analysis we found 308 significantly associated (p<0.05) CNVRs in the Indian data. These POAG associated CNVRs were enriched in nervous system development. 113 CNVRs (37%) were significantly associated with the Caucasian data set. These contain 5 genes previously reported in eye diseases, namely, IDUA, FOXE3, NDUF7, PRPF6 and WNT3. We also found 6 associated CNVRs in previously known glaucoma loci.ConclusionWe have shown that common CNVRs are significantly associated in both datasets irrespective of the population background. We have also identified candidate genes/regions which are uniquely present in POAG cases and absent in controls. Our data might provide new insights into role of CNV in pathogenesis of POAG