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Alistair J Barber, Zeinab Nasralah; Photoreceptor distortion accompanies inner retina degeneration and loss of visual function in streptozotocin-diabetic rats. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3201.
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© ARVO (1962-2015); The Authors (2016-present)
This study aimed to measure retinal cell layer thicknesses in diabetic and control Long-Evans rats by spectral-domain optical coherence tomography (OCT) and compare these changes with deficits in visual function. The study also assessed cell death and synaptophysin expression, which may also correspond to functional changes in vision.
Male Long-Evans streptozotocin-diabetic rats (STZ, 100 mg/kg, pH 4.5, i.v., n=9) were compared to age-matched controls (CNT, n=10). All procedures were in accordance with the Penn State Hershey College of Medicine IACUC and the ARVO guidelines for animal use in ophthalmology research. Spatial frequency threshold (SFT) and contrast sensitivity (CS) were measured using behavioral optokinetic testing (Optomotry) 6 and 10 weeks after STZ injection. Retinal layer thicknesses were measured by OCT in four separate regions of each retina after 15 weeks of diabetes. Apoptosis was measured by cell death ELISA and relative synaptophysin content was measured by immunoblotting. Statistical comparisons were by t-test with p<0.05 considered a significant difference.
SFT and CS were significantly reduced in STZ rats compared to CNT at both time points (p<0.001). The inner plexiform layer was 10.5% thinner in the STZ rats compared to CNT (p<0.05). The thicknesses of the inner nuclear and outer plexiform layers in STZ rats were not different from CNT. In contrast, the outer nuclear layer was 10.8% thicker in STZ rats compared to CNT (p<0.01) but the combined thickness of the outer nuclear layer and outer segments was unchanged across groups, suggesting a reduction in outer segment length. By subtraction the outer segment length was 17% less in STZ rats compared to CNT (p<0.01). There was also a significant increase in apoptosis (p<0.001) and significant reduction in synaptophysin content (p<0.05) in STZ rats compared to CNT.
Diabetes-induced thinning of the inner plexiform layer accompanied by reduction in synaptophysin content and reduced contrast sensitivity suggest a loss of synapses in the inner retina. Apoptosis is also likely to contribute to the loss of function. Shortening of the photoreceptor outer segments may be due to compression caused by expansion of the outer nuclear layer, presumably from vascular permeability-derived edema. The photoreceptor distortion is also likely to contribute to reduced visual function.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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