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Marina V Yasvoina, Almas Dawood, Michael B. Powner, Marcus Fruttiger; Upregulation of activated Müller cell marker independent of local ischemia in diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5193. doi: https://doi.org/.
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Microvascular abnormalities and non-perfusion underlie deterioration of the retina and progressive loss of vision in diabetic retinopathy (DR). However, ischemia is usually not panretinal, but rather affects clearly localised regions. How well non-perfused and perfused retinal regions correlate with neural changes in DR within the same eye has not been well studied. Here, we present a case study describing the spatial relationship between vascular degeneration and neuronal/glial changes in a post-mortem retina with DR.
Post-mortem donor tissue was obtained through the Moorfields Eye Bank. The donor age ranged between 39 and 80 years (mean age 58 years). A total of 6 eyes from patients diagnosed with diabetes were histologically assessed for evidence of vessel damage by staining retinal blood vessels with UEA agglutinin in retinal wholemounts. One eye was found with apparent proliferative DR (evidence of laser scars) and regions of severe vascular dropout. This specimen was further studied and compared to a healthy eye and a diabetic case with no vascular pathology. The specimen was paraffin embedded and serially sectioned. The distribution of blood vessels within sections was then used to establish the exact position within the wholemount. Further sections were immunostained with a panel of antibodies for neural, glial and vascular proteins (Crystallin alpha A, Collagen IV, CRALBP, GFAP, Glutamine Synthetase, MAP2, Opsin, Rhodopsin, Vimentin).
As expected, a localised region with loss of blood vessels showed severe hypotrophy due to a complete loss of inner retinal cells. However, photoreceptors were also reduced in this region. Interestingly, Crystallin alpha A was markedly upregulated compared to controls throughout the retina, independent of localised vascular loss.
In this case of DR, our detailed histopathological analysis identified evidence of reactive Müller cells (Crystallin alpha A upregulation) throughout the retina, demonstrating that neural changes can occur in the diabetic retina independent of blood vessels loss. Further DR specimens will have to be studied to confirm this and to establish effects on neurons in more detail. Understanding early pathological changes in DR, will provide insight into disease mechanisms and may also reveal therapeutic targets.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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