Experimental rationale for the use of thioctic acid and indomethacin in the therapy of the early stage of retinal neurodegeneration

Abstract

Purpose: to assess the possibility of using thioctic acid and indomethacin tin eyedrops for the therapy of early stages of retinal neurodegeneration.Material and methods. The study was performed on 20 Chinchilla rabbits, including 16 rabbits in whom the neurodegenerative process in the retina was produced by intravitreal installation of 6-hydroxydopamine (6-OHDA), 0.25 mg per eye, and 4 rabbits (8 eyes) served as control. Thioctic acid 0.5% and Indocollir 0.1% were instilled separately and in combination 5 times daily for 7 days after the injection of 6-OHDA. Pupillary light reaction was estimated and eye fundus condition analyzed. Alpha2-macroglobuline ( 2-MG) and SOD activity, dopamine and protein concentrations were measured in retinal homogenates.Results. Instillations of thioctic acid reduced the retinal damage area almost by half as compared to the untreated group (p d 0.005). Indomethacin was less effective, but the combination of the two drugs brought about a maximal reduction of the damage area (p d 0.05 against the untreated group). Both preparations normalized the disturbed pupillary light reaction. The injection of 6-OHDA caused a decrease of dopamine concentration in the retina (0.050 ± 0.009 pg/mg as against 0.095 ± 0.031 pg/mg in healthy controls, р d 0,05). After instillations of indomethacin and thioctic acid, the concentration tended to increase, and it increased significantly after treatment with their combination (0.141 ± 0.037 pg/mg, p d 0.01 as against untreated animals). The activity of 2-MG in retina decreased after a 6-OHDA injection (2.93 ± 0.42 pg/mg as against 5.5 ± 1.2 pg/mg in healthy controls, р < 0 005) just as they increased the decreased SOD (13.30 ± 5.68 U/mg in healthy controls, 5.41 ± 1.50 U/mg in untreated animals, р < 0.05). Both preparations applied separately or in combination caused a significant increase of 2-MG activity (thioctic acid — 4.19 ± 0.91 pg/mg, indomethacin — 6.95 ± 1.09 pg/mg, combination — 7.25 ± 0.63 pg/mg, р < 0.05 as against the untreated animals) and SOD activity (thioctic acid — 8.25 ± 1.27 U/mg, indomethacin — 29.84 ± 6.63 U/mg, combination — 23.99 ± 3.78 U/mg, р < 0.01 as against the untreated animals).Conclusion. The combination of indomethacin and thioctic acid in eyedrops is the most effective for the prevention of eye damage caused by 6-OHDA, which makes this method promising for the treatment of eye diseases accompanied by neurodegeneration.