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

doi:10.1186/s12974-021-02263-3

Journal of Neuroinflammation (Sep 2021)

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

Affiliations

Francesca Lazzara: Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, School of Medicine, University of Catania
Rosario Amato: Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami
Chiara Bianca Maria Platania: Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, School of Medicine, University of Catania
Federica Conti: Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, School of Medicine, University of Catania
Tsung-Han Chou: Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami
Vittorio Porciatti: Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami
Filippo Drago: Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, School of Medicine, University of Catania
Claudio Bucolo: Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, School of Medicine, University of Catania

DOI: https://doi.org/10.1186/s12974-021-02263-3
Journal volume & issue: Vol. 18, no. 1
pp. 1 – 19

Abstract

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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.

Published in Journal of Neuroinflammation

ISSN: 1742-2094 (Online)
Publisher: BMC
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry: Neurology. Diseases of the nervous system
Website: https://jneuroinflammation.biomedcentral.com/

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