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

Francesca Lazzara, Rosario Amato, Chiara Bianca Maria Platania, Federica Conti, Tsung Han Chou, Vittorio Porciatti, Filippo Drago, Claudio Bucolo

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number206
JournalJournal of Neuroinflammation
Volume18
Issue number1
DOIs
StatePublished - Dec 2021

Keywords

  • Calcitriol
  • Cytokines
  • Glaucoma
  • Inflammation
  • Retina
  • Vitamin D

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology
  • Neurology
  • Cellular and Molecular Neuroscience

Fingerprint

Dive into the research topics of '1α,25-dihydroxyvitamin D<sub>3</sub> protects retinal ganglion cells in glaucomatous mice'. Together they form a unique fingerprint.

Cite this