Early Microvascular and Oscillatory Potentials Changes in Human Diabetic Retina: Amacrine Cells and the Intraretinal Neurovascular Crosstalk

Edoardo Midena,Luisa Frizziero,Elisabetta Pilotto,Giulia Midena,Tommaso Torresin,Evelyn Longhin

doi:10.3390/jcm10184035

Abstract

To analyze the early microvascular retinal changes and oscillatory potentials alterations secondary to diabetic retinal damage, 44 eyes of 22 diabetic patients without and with mild diabetic retinopathy (DR) and 18 eyes of 9 healthy controls were examined. All subjects underwent spectral domain optical coherence tomography (SD-OCT), OCT angiography (OCTA), and electroretinography of oscillatory potentials (OPs). At OCTA, vessel area density (VAD), vessel length fraction (VLF), and fractal dimension (FD) were significantly reduced in the superficial vascular plexus (SVP), VLF and FD in the intermediate capillary plexus (ICP), and FD in the deep capillary plexus (DCP) in the diabetic group compared to the control group. The amplitude (A) of OP2, OP3, OP4 and the sum of OPs were significantly reduced in the diabetic group versus the controls, and the last two parameters were reduced also in patients without DR versus the controls. Moreover, in the diabetic group, a significant direct correlation was found between the A of OP1, OP2, OP3 and sOP and the VLF and FD in the SVP, while a statistically significant inverse correlation was found between the A of OP3 and OP4 and the VDI in the ICP and DCP. The reduced oscillatory potentials suggest a precocious involvement of amacrine cells in diabetic eyes, independently of DR presence, and their correlation with vascular parameters underlines the relevance of the crosstalk between these cells and vascular components in the pathophysiology of this chronic disease.

Highlights

As regards the OCT angiography (OCTA) results, no significant difference was found in the FAZ area of superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP) between the diabetic and the control group
Using OCT, OCTA, and oscillatory potentials (OPs), the present study found that both retinal structural and vascular changes as well as functional ones are precociously present in diabetic eyes, compared to healthy controls, in accordance to previous reports, and that they are related to each other [14,19]
We found a reduction of vessel length fraction (VLF) and fractal dimension (FD) of the intraretinal vascular networks at OCTA, representing the length and complexity of retinal microvessels, in diabetic patients with no or early signs of diabetic retinopathy (DR), as previously reported [14]

Summary

Introduction

Retinal microvascular damage has been considered the main pathophysiological driver of retinal damage induced by diabetes, including endothelial cell damage, pericyte loss, and secondary breakdown of the blood–retinal barriers [2]. Some studies have shown that a systemically impaired glucose metabolism causes early dysfunction in the neural retina [3]. Even if an impairment of neurovascular coupling in the retina of patients with diabetes has been reported even before clinically visible DR, the crosstalk among vessels, neurons, and glial cells in the retina is still partly unknown, as well as its contribution to retinal damage secondary to diabetes [3,4,5,6]. Electroretinography (ERG) has shown to detect early neuronal abnormalities, before clinically detectable

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