Neuroprotective Effect of Subconjunctival Melatonin Injections in 6-Hydroxydopamine-Induced Neurotoxic Eye Damage

The search for new effective methods of neuroprotection is relevant for the treatment of a wide range of common eye diseases such as age-related macular degeneration, glaucoma, and diabetic retinopathy. Using a rabbit model of neurotoxic eye damage induced by intravitreal injection of the dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA), we studied the effect of subconjunctival injections of 0.1% melatonin solution on pathophysiological and biochemical processes in the eye. Administration of 6-OHDA caused destruction of the retinal pigment epithelium, narrowing of retinal vessels, hemorrhages, decrease in ocular blood flow, and intraocular pressure, as well as reduced activity of α₂-macroglobulin and concentrations of matrix metalloproteinase-9 and angiotensin-converting enzyme in the aqueous humor, vitreous body, and retina. Subconjunctival melatonin injections over 9 days resulted in the 2-fold on average reduction of the area of retinal damage, and normalization of the minute volume of ocular blood flow and intraocular pressure. On day 14, an increase in the α₂-macroglobulin activity in the aqueous humor (0.66 ± 0.19 vs. 0.49 ± 0.13 nmol/min per 1 mg protein) and vitreous body (0.50 ± 0.15 vs. 0.21 ± 0.07 nmol/min per 1 mg protein, p < 0.05) was observed, along with a decrease in the matrix metalloproteinase-9 concentration (118.4 ± 34.6 vs. 524.3 ± 163.2 ng/mg, p < 0.05) and angiotensin-converting enzyme concentration (371.0 ± 52.1 vs. 596.1 ± 171.5 ng/mg, p < 0.05) in the retina. This indicates reduction in the intensity of inflammation and vascular wall permeability. Melatonin could be considered a promising neuroprotective component in the complex therapy of retinal diseases.