Abstract
Purpose :
Retinal horizontal cells (HC) are neuromodulatory cells that form lateral connections between rod and cone photoreceptors and bipolar cells, and contribute to suppressive rod-cone interactions via their direct connections between rods and cones and through inhibitory input to receptive fields. However, despite their key role in visual processing, their contribution to visual dysfunction in disease has never been investigated. I recently developed an ERG protocol that reflects HC loss in a rat model of traumatic brain injury (TBI). Herein I describe the results of testing this protocol in humans and the clinical conditions that produce HC ERG abnormalities.
Methods :
The HC ERG paradigm consists of comparing the amplitudes of 2 full-field ERGs that reflect cone function: one in which a light (1 cd.s/m2) is flashed over a dim background (1 cd/m2), and the other using the same light flash superimposed on a bright background (30 cd/m2). In order to enable rod suppression of cones, all testing must be conducted in a dark-adapted individual without any exposure to a preconditioning background.
Results :
If the retina responds linearly to these conditions, the ERG amplitudes should reflect the difference in luminance contrasts. However, in visually-normal patients, the ratio of the ERG b-wave amplitudes recorded on the dim:bright backgrounds was only slightly larger than 1, very similar to data from normal rats (X1 – X2 = 0.06, p = 0.48, t-test). 27 patients with 16 different diagnoses were tested. Of these patients, 3 diagnoses produced ratios that exceeded the normal range and were as high as 3 times the normal mean: TBI (1 patient), vigabatrin toxicity (2 patients), and rod dystrophy (2 patients). In addition, there were 3 patients with unknown diagnoses who had abnormal ratios.
Conclusions :
An ERG protocol was developed that reflects a lack of suppressive rod-cone interaction. As rod inhibition of cones is modulated by horizontal cells, this analysis also reflects HC function. Results from the TBI patient were similar to those from a TBI rat model. The anti-seizure drug vigabatrin increases extracellular levels of GABA and has been shown to be most toxic to cells like HC who have a high density of GABA receptors. As proof of principal, 2 patients with rod dystrophies had elevated ratios, presumably because rod function, and its inhibition of cones, was subnormal, and not because of HC cells per se.
This is a 2020 ARVO Annual Meeting abstract.