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Michael O'Hare, Gema Esquiva, Mary McGahon, Jennifer Henry, Richard Knell, David Grieve, Graham McGeown, Tim Curtis; TRPV2 heterozygous knockout rats display diabetic retinopathy-like lesions. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3006. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
In diabetic subjects retinal blood flow autoregulation has been shown to be disrupted prior to the onset of clinically evident retinopathy. Our recent data has suggested that stretch-activated TRPV2 channels play a critical role in blood flow autoregulation in the retina and that their expression and activity is disrupted in diabetes. In the present study, we have examined whether TRPV2 heterozygous (+/-) rats develop retinal lesions characteristic of diabetic retinopathy.
TRPV2 WT (+/+) and TRPV2+/- rats were assessed for retinal pathology at P20, P90 and P360. Immunolabelling was carried out on flat-mounted retinas and retinal cryosections to study the vascular, neuronal and glial components of the retina. Vasopermeability was assessed using the Evan’s blue dye method and systemic blood pressure measured using tail cuff plethysmography. Retinal neurophysiology was examined by electroretinography (ERG).
Blood glucose, haemoglobin A1c and systemic blood pressure were within normal ranges for both TRPV2 WT and TRPV2+/- animals. There was no evidence of retinal pathology in TRPV2 WT or TRPV2+/- animals at P20. At P90 and P360, however, TRPV2+/- animals exhibited a significant increase in vasopermeability (P<0.05) and acellular capillary formation (collagen IV positive/Isolectin B4 negative vessels; P<0.05) when compared to their WT counterparts. A decrease in the mean number of retinal ganglion cells (p<0.001) and an increase in the proportion of activated Müller glia (GFAP-positive; p<0.0001) was also observed. In addition, microglial cell numbers were increased in P90 and P360 TRPV2+/- retinas (P<0.05 & P<0.01 respectively), suggesting pro-inflammatory changes. TRPV2+/- animals showed progressive neurophysiological dysfunction, manifesting as a reduction in the amplitude of both the ERG A & B-waves at P360 (P<0.01).
TRPV2 heterozygous rats exhibit microvascular pathology in the absence of any changes in blood glucose or systemic blood pressure. Our data suggest that disruption of TRPV2 channel activity and blood flow autoregulation in the retina may contribute to the pathogenesis of diabetic retinopathy.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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