Alterations in Retinal Neuronal Structure, Function and Involvement of Inflammation in the Long Term Diabetic Rat

Abstract

Purpose: : Pathological changes in diabetic retinopathy involves both neuronal and microvascular damages. Chronic inflammation has been long suspected to play a role in the pathogenesis. This study evaluated the change of retinal structure and function, and the levels of pro-inflammatory factors in the retinas of rats subjected to long term (11-month) streptozotocin (STZ)-induced diabetes.

Methods: : After 11 months of diabetes, STZ-diabetic (STZD) male Lewis rats were compared with their age-matched non-diabetic (ND)controls on 1) retinal function via electroretinogram (ERG); 2) retinal structure via measuring retinal layer thickness on paraffin-embedded eye cross section and total retinal ganglion cell (RGC) counts (using the RGC marker Brn-3a) on retinal flatmount; and 3) levels of the pro-inflammatory factors IL-1β, NF-ΚB, and ICAM-1, via elisa.

Results: : Amplitudes of a, b wave and oscillatory potentials, OP₂ and OP₅ in particular, from STZD rats were significantly lower than those from ND control (44%, 58%, 60% and 53% respectively, P<0.05). Inner and outer nuclear layers were significantly thinner in the STZD than in ND (P<0.05). Damage to photoreceptor inner and outer segments was also observed. However, RGC counts showed no difference between two groups. Significantly higher retinal levels of ICAM-1 (3 fold), IL-1β (7 fold) and NF-ΚB (2 fold) were observed in STZD rats compared with their age-matched controls.

Conclusions: : Profound damage to the structure and function of the neural retina was observed after 11 months of diabetes, but, in contrast to numerous previous reports, no ganglion cell loss was observed. This may be due to the use here of a highly specific marker to identify ganglion cells. Upregulation of markers of inflammation was observed in these long-term diabetic animals, confirming a role for inflammation in diabetic retinopathy.

Keywords: diabetic retinopathy • inflammation • electroretinography: non-clinical