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Sean Donghyun Kim, Phoebe Nguyen, basma baccouche, Wei Wei Wang, Jeffrey Sundstrom, Alistair J Barber; Corneal nerve fiber morphology and neurodegeneration of the retina in diabetic rats. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5191.
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© ARVO (1962-2015); The Authors (2016-present)
Diabetes-induced degeneration of the inner retina occurs in both animals and humans. Recent clinical evidence suggests that corneal nerve fibers may also degenerate in diabetes. The aim of this study was to compare retinal cell layer thickness, using spectral domain optical coherence tomography (SD-OCT), with corneal nerve density, in streptozotocin (STZ)-diabetic rats.
Long-Evans rats were made diabetic by STZ injection (100 mg/kg, i.v., n=6) and compared to age-matched controls (n=6). Retinal morphology was measured by SD-OCT (Envisu 2210, Bioptigen) 9 weeks later. Rats were sacrificed after 10 weeks of diabetes and corneas were dissected, labeled for β-tubulin and flat-mounted for confocal microscopy (Leica SP8). Images from 5 random 116.25 µm2 regions were obtained. Corneal nerve fiber density (number/mm2) and corneal nerve fiber length (mm/mm2) were measured by image analysis using Neuron J. Statistical comparisons were made by two-tailed t-test with p<0.05 considered significant (Prism, Graphpad). Degeneration was also confirmed by cell death ELISA on one retina from each rat.
There was significantly more cell death in STZ-diabetic rat retinas compared to controls (p<0.05). SD-OCT data revealed that the inner plexiform and inner nuclear layers were significantly thinner in the STZ-diabetic rats compared to controls (p<0.05 and p<0.01 respectively), while the outer nuclear and photoreceptor layers were significantly thicker (p<0.001 and p<0.05 respectively). Morphological analysis of the corneal nerve fibers revealed no significant differences between STZ-diabetic and control groups.
Cell death and reduction of the inner plexiform and nuclear layers indicate neurodegeneration with a potential loss of synaptic connectivity, as established previously. Thickening of the outer nuclear and photoreceptor layer is most likely due to fluid accumulation caused by increased permeability of the blood retinal barrier, or possibly by increased resistance to fluid clearance through the pigment epithelium. This study found no significant difference in the corneal nerve fiber morphology, suggesting that this degeneration cannot be detected in rats after 10 weeks of diabetes. Together our data suggest that inner retinal degeneration and outer retinal swelling occur in parallel during the first 2-3 months of STZ-diabetes but is not accompanied by changes in corneal neuron morphology.
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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