Delay of oscillatory potentials links animal models to diabetes in the human eye

Abstract

Purpose : Diabetic retinopathy is a major cause of vision loss worldwide. In both human disease and animal models, electroretinography (ERG) can detect functional losses resulting from diabetic eye complications. However, there is no consensus which parameters of ERG have robust predictive value on disease progression. To address this, we studied spontaneous type-2 and induced type-1 models to establish systematic alterations of ERG parameters by diabetes.

Methods : Electroretinographs were recorded 9 weeks after hyperglycemia onset in 5 rat phenotypes: (1) spontaneously diabetic BBZDR/Wor, (2) pre-diabetic BBZDR/Wor (3) non-diabetic BBZDR/Wor,(4) streptozotocin (STZ)-treated Brown-Norway (BN), and (5) sham-treated BN controls. Dark-adapted (DA) ERG (8 flash intensities from 0.003 -10 cd*s/m²) and c-waves (100 ms pulse at 225 cd/m²) were measured in a Diagnosys Colordome system. Light-adapted (LA) ERG (3 cd*s/m² with 30 cd/m² background after 5 min adaptation with 30 cd/m² light) and flicker-responses (3 cd*s/m² with 30 cd/m² background at 10-40 Hz) were collected in a Diagnosys Celeris instrument.

Results : Similar results were obtained in the type-2 diabetic BBZDR/Wor model and the STZ-treated type-1 diabetic model. In both, DA and LA oscillatory potential (OP) latencies were significantly delayed by diabetic conditions. Moreover, DA OP latencies segregated by disease severity in the BBZDR/Wor animals. Likewise, conditions of diabetes also delayed c-wave latencies for both. However, DA a- and b-wave amplitudes/latencies, c-wave amplitudes, and DA OP amplitudes exhibited no significant changes for either. A reduction of LA OP amplitudes was observed only in diabetic BBZDR/Wor rats but not in STZ-treated BN rats.

Conclusions : These data are consistent with human studies suggesting that a delay of oscillatory potentials is an indicator of diabetes even if common symptoms of retinopathy cannot be observed. The strong, quantitative agreement of results in the two models underlines the value of ERG testing as an early detection technique for DR in humans. Our results pave the way to a systematic understanding of ERG changes due to hyperglycemia alone as well as other mechanisms common to both types of diabetic disease.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

 

Light intensity-response in type-2 and type-1 rat models of diabetes. Experimental error is smaller than the respective marks. BN: Brown-Norway, STZ: streptozotocin