Serotonin Signaling Pathway Modulation Affects Retinal Neuron Survival in Experimental Model of Retinal Ischemia

Serotonin is a key neurotransmitter involved in visual processing. Selective serotonin reuptake inhibitors (SSRIs), such as Escitalopram, enhance serotonergic transmission and exert neuroprotective effects. Although these actions are well established in the central nervous system, their influence on retinal neurons remains unclear. This study investigated whether Escitalopram provides neuroprotection to retinal neurons following ischemic injury. Rats received Escitalopram or vehicle for 12 weeks. Retinal ischemia was induced by unilateral episcleral vein cauterization. A subset of animals received a retrobulbar injection of meclofenamic acid (MFA). Retinal function was assessed using electroretinography, intraocular pressure (IOP) was monitored, and retinas were collected for immunofluorescence and Western blot. Cauterization increased IOP in both groups, inducing retinal blood flow disturbances. Immunofluorescence showed a reduced number of retinal ganglion cells after cauterization, which was alleviated by SSRI treatment. Escitalopram also elevated expression of the brain-derived neurotrophic factor. Electroretinography revealed improved photopic negative response (PhNR) amplitudes in Escitalopram-treated rats, indicating improved retinal ganglion cell function. Following MFA, PhNR remained stable in SSRI-treated animals, whereas a significant impairment was observed in the vehicle-treated group. These findings demonstrate that Escitalopram provides neuroprotection by reducing both functional and structural damage in the retina and may represent a promising therapeutic strategy for retinal neurodegeneration.