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Andrew T C Tsin, Tianle Zou, Richard LeBaron, Veronica Gonzalez-Fernandez, Pamela Hires, John Lonsdale, Federico Gonzalez-Fernandez; Differential Expression of IRBP, Albumin, BIGH3 and PNA Binding in the Interphotoreceptor Matrix Versus Choroid in Diabetes, AMD and Glaucoma. Invest. Ophthalmol. Vis. Sci. 2014;55(13):6013. doi: https://doi.org/.
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Interphotoreceptor retinoid-binding protein (IRBP) is a 145 kDa glycolipoprotein originally described in the vitreous, and interphotoreceptor marix (IPM). Interestingly, its concentration in the vitreous is reduced in early stages of diabetic retinopathy (Garcia-Raminez et al, Diabetologia, 52:2633, 2009). In the retina, IRBP is restricted to the subretinal space. Our long-term goal is to understand the mechanism, and significance for the reduced vitreous IRBP in diabetes.
We used immunohistochemistry to compare the distribution of IRBP and peanut agglutinin (PNA), with that of the extracellular choroidal proteins albumin, and BIGH3 (Transforming β induced gene-human clone 3, or Betanectin). Globes were retrieved from 32 donors (30 to 98 yrs) with diabetes, age related macular degeneration (AMD), glaucoma, and normal controls. The interval between death and placement of the eye in formalin was under 10.5 hrs except in one control. For all cases, a detailed gross and histopathological study was performed, and correlated with clinical history. Cases: Diabetes (2 no apparent diabetic retinopathy, 4 non-proliferative, 2 proliferative); AMD (5 dry, 2 wet); glaucoma (11 cases), and normal controls (6 cases). Nine had more than one diagnosis.
Except when the postmortem interval was beyond about 12 hrs, IRBP was restricted to the IPM, and albumin to the choroid. However, in diabetes, IRBP was present in the choroid, and was reduced in the IPM in proportion to disease severity, and albumin was present in the IPM. In contrast, no significant IRBP was found in the choroid of patients with AMD, or glaucoma except when diabetes was also present. In AMD and glaucoma, decreased IPM IRBP was noted whenever there was photoreceptor degeneration. BIGH3 and PNA labeling did not show evidence for diffusion out of the choroid or IPM, respectively.
Reduced expression of IPM IRBP, and its appearance in the choroid was characteristic of diabetes compared to AMD, glaucoma or normal controls. The concomitant movement of albumin into the IPM is consistent with reduced RPE integrity. The lack of redistribution of BIGH3 and PNA binding glyconjugates may be due to local binding to choroidal integrins, or the IPM hyaluronan scaffold, respectively. Our data suggests that increased clearance of IRBP may contribute to decreased vitreous IRBP in diabetes.
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