Evaluation of the Neuroprotective Efficacy of Intravitreal Adalimumab Injection in Experimental Rabbit Glaucoma Model

Project no. 28495 · Status: Kapanmış (Yayın bekleniyor) · 2023

Summary

Purpose: The aim of the study is to create a microbead induced ocular hypertension (OHT) model in rabbits and to evaluate the effects of intravitreal and intraperitoneal injections of Adalimumab (ADA) on the number of retinal ganglion cells (RGC), retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness.Materials and Methods: 15 rabbits of New Zelland strain were randomized into 4 groups. OHT was induced with microbead injection into the anterior chamber of right eyes. On 7th, 14th days of OHT, ADA was injected at one of two concentrations (group 1-G1:2,5mg /group 2-G2:5mg) into two groups, intraperitoneally 5mg/kg into the third group (G3), and balanced salt solution into fourth group (sham). The left eyes were used as controls. Retinal and optic nerve head (ONH) histology was studied with Hematoxylin-eosin and Toluidine blue staining. measurements were evaluated using QuPath and ImageJ software, and ONH-RNFL measurements were evaluated by Spectral Domain Optical Coherence Tomography.Results: OHT was induced in a total of 13 eyes. Two rabbits were excluded (endophthalmitis, total hyphema). The average pre-OHT IOP from all eyes 9,7±0,9(8-11) mmHg and was found to be compatible with the literature (10,8±1,1, p0,05). Statistically significant IOP increase was observed in all subject eyes on day 7 (14±1,4 (12-18) mmHg) (p=0,01) and maintained until ADA injection. RGCs in the eyes with elevated IOP were 7,2±1,2(5-9) and 7,6±1,5(6-9), 6,3+1.1(5-7) cells per 500 µm² in ADA treated groups, G1, G2, G3, respectively. There was no statistically significant difference between treatment groups. The mean RNFL was 125,9±10,9(113,9-135,3) µm in controls, 60,2±9,4(50,1-71,7) µm in G1, 45,7±2,9(43.4-49.1) µm in G2, 22,8±2,9(19,7-25,4) µm in G3, 21,7±10(10,1-27,4) µm in sham. While a decrease in RNFL was observed in all groups, significant elevations were observed in G1 and G2 (p= 0.01). The mean GCC of controls was 45,5±1,9(43,4-48,1) µm, G1 41,2±2,2(39,5-44,8) µm, G2 39,3±3,3 (36,3-43,5) µm, G3 34,1±1,6 (32,3-35,3) µm, sham was 38,3±1,1(37,1-39,4) µm. While a decrease in GCC was observed in all groups, significant increase was observed in G1 compared to other groups. (p = 0.01).Conclusions: In the study, neuroprotective effect was observed on RNFL and GCC with intravitreal ADA therapy. Especially low-dose (2,5 mg) ADA treatment provides prominent results in GCC protection. These findings may further contribute to the literature for a new treatment strategy for glaucoma using TNF-α antagonists or inflammation suppressors.

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