1α,25-dihydroxyvitamin D₃ protects retinal ganglion cells in glaucomatous mice.

ABSTRACT:

Background

Glaucoma is an optic neuropathy characterized by loss of function and death of retinal ganglion cells (RGCs), leading to irreversible vision loss. Neuroinflammation is recognized as one of the causes of glaucoma, and currently no treatment is addressing this mechanism. We aimed to investigate the anti-inflammatory and neuroprotective effects of 1,25(OH)₂D₃ (1α,25-dihydroxyvitamin D₃, calcitriol), in a genetic model of age-related glaucomatous neurodegeneration (DBA/2J mice).

Methods

DBA/2J mice were randomized to 1,25(OH)₂D₃ or vehicle treatment groups. Pattern electroretinogram, flash electroretinogram, and intraocular pressure were recorded weekly. Immunostaining for RBPMS, Iba-1, and GFAP was carried out on retinal flat mounts to assess retinal ganglion cell density and quantify microglial and astrocyte activation, respectively. Molecular biology analyses were carried out to evaluate retinal expression of pro-inflammatory cytokines, pNFκB-p65, and neuroprotective factors. Investigators that analysed the data were blind to experimental groups, which were unveiled after graph design and statistical analysis, that were carried out with GraphPad Prism. Several statistical tests and approaches were used: the generalized estimated equations (GEE) analysis, t-test, and one-way ANOVA.

Results

DBA/2J mice treated with 1,25(OH)₂D₃ for 5 weeks showed improved PERG and FERG amplitudes and reduced RGCs death, compared to vehicle-treated age-matched controls. 1,25(OH)₂D₃ treatment decreased microglial and astrocyte activation, as well as expression of inflammatory cytokines and pNF-κB-p65 (p < 0.05). Moreover, 1,25(OH)₂D₃-treated DBA/2J mice displayed increased mRNA levels of neuroprotective factors (p < 0.05), such as BDNF.

Conclusions

1,25(OH)₂D₃ protected RGCs preserving retinal function, reducing inflammatory cytokines, and increasing expression of neuroprotective factors. Therefore, 1,25(OH)₂D₃ could attenuate the retinal damage in glaucomatous patients and warrants further clinical evaluation for the treatment of optic neuropathies.

SUBMITTER: Lazzara F 

PROVIDER: S-EPMC8444391 | biostudies-literature |

REPOSITORIES: biostudies-literature