id_923. IMPACT OF SELECTIVE SYNAPTIC TRANSMISSION BLOCKADE ON VISUAL SIGNAL CONDUCTION AND OXIDATIVE STRESS IN THE RAT RETINA
Monika Katan1,2, Anna Pacwa1,2,3,4, Anna Gąsiorek1,2, Klaudia Bugara1,2, Bartosz Machna1,2, Joanna Lewin-Kowalik1,2,3, Adrian Smędowski1,2,3,5,6
1 Medical University of Silesia, Laboratory for Translational Research in Ophthalmology, Department of Ophthalmology, Faculty of Medical Sciences in Katowice, Katowice, Poland
2 Medical University of Silesia, Department of Ophthalmology, Faculty of Medical Sciences in Katowice, Katowice, Poland
3 Glaucotech Co, Katowice, Poland
4 Medical University of Silesia, Department of Clinical Genetics and Rare Diseases, Faculty of Medical Sciences in Katowice, Katowice, Poland
5 Medical University of Silesia, Department of Ophthalmology, Professor K. Gibinski University Clinical Center, Faculty of Medical Sciences in Katowice, Katowice, Poland
6 Medical University of Silesia, Department of Paediatric Ophthalmology, Faculty of Medical Sciences in Katowice, Katowice, Poland
INTRODUCTION: Disturbances in retinal synaptic transmission may contribute to neurodegenerative processes and alter bioelectrical responses of the visual system.
AIM(S): This study investigated the effects of selective blockade of retinal synaptic transmission on visual evoked potentials (VEP) and oxidative stress markers in rats.
METHOD(S): The study included 40 Long Evans rats. VEP were recorded before and after intravitreal administration of pharmacological modulators targeting glutamatergic (AMPA, NMDA, mGluR6), GABAergic, and electrical synapses. VEP latency and amplitude were analyzed, and retinas were subsequently collected for immunofluorescence assessment of oxidative stress markers (4-HNE, 8-OHdG).
RESULTS: Selective synaptic modulation induced pathway-specific changes in VEP parameters. AMPA receptor blockade caused marked VEP latency prolongation (~31%) and amplitude reduction (~43%). NMDA receptor blockade resulted in a pronounced amplitude decrease (~55%) accompanied by latency shortening (~14%). GABAergic modulation led to strong amplitude reduction (~56%) and moderate latency prolongation (up to ~20%), whereas mGluR6 modulation produced milder effects. Retinal levels of the lipid peroxidation marker 4-HNE were significantly increased after AMPA, NMDA and GABAergic blockade (p < 0.0001), indicating enhanced oxidative damage associated with disrupted synaptic transmission. In contrast, the DNA oxidation marker 8-OHdG was reduced after NMDA receptor blockade and GABAergic modulation (p < 0.0001), suggesting predominance of early lipid-related oxidative responses.
CONCLUSIONS: Selective interference with retinal synaptic transmission leads to measurable functional alterations along the visual pathway accompanied by pathway-specific oxidative stress responses. The combined use of VEP recordings and oxidative stress markers provides a sensitive approach for assessing retinal synaptic dysfunction.