CD40-CD154 Interactions Induced Progressive Neurodegeneration in Acute Ocular Hypertension Mice

This study aimed to investigate the role and mechanism of CD40-CD154 interaction in acute ocular hypertension-induced progressive retinal inflammation and damage.

Transmission electron microscopy was used to observe the optic nerve of C57BL/6 mice at different time points of acute ocular hypertension and the sham group, and Western blotting was used to examine the relative expression of CD40 and CD154 at different time points. Knocking down CD40 and CD154 with CD40 and CD154 small interfering RNA, respectively, glaucomatous neural damage was assessed by using axon counts and observed by transmission electron microscopy imaging of the optic nerve. Immunofluorescence was used to determine the localization of CD154 and CD40 in the retinas of mice and flow cytometry was used to detect the expression of CD154 and CD40 and the subpopulation distribution of CD4+ T cells in mice spleens.

Axon loss continued after the high IOP of modeling mice returned to the normal range. The CD40 and CD154 expressions increased in glaucomatous mice. Compared with the 7-day group, the number of axons largely increased after CD40 or CD154 was knocked down. CD40 and CD154 were coexpressed in the retina. The trend of subpopulation distribution of T cells, especially Th1 cells in the spleens, was consistent with the expression of CD40 and CD4+CD154+.

CD40-CD154 interaction contributes to progressive glaucomatous neurodegeneration after the elevated IOP returns to the normal range. T helper type 1 cells play a key role in the damage of glaucomatous mice.