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Melatonin Prevents Non-image-Forming Visual System Alterations Induced by Experimental Glaucoma in Rats

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Abstract

Glaucoma is a blindness-causing disease that involves selective damage to retinal ganglion cells (RGCs) and their axons. A subset of RGCs expressing the photopigment melanopsin regulates non-image-forming visual system functions, such as pupillary light reflex and circadian rhythms. We analyzed the effect of melatonin on the non-image-forming visual system alterations induced by experimental glaucoma. For this purpose, male Wistar rats were weekly injected with vehicle or chondroitin sulfate into the eye anterior chamber. The non-image-forming visual system was analyzed in terms of (1) melanopsin-expressing RGC number, (2) anterograde transport from the retina to the olivary pretectal nucleus and the suprachiasmatic nuclei, (3) blue- and white light-induced pupillary light reflex, (4) light-induced c-Fos expression in the suprachiasmatic nuclei, (5) daily rhythm of locomotor activity, and (6) mitochondria in melanopsin-expressing RGC cells. Melatonin prevented the effect of experimental glaucoma on melanopsin-expressing RGC number, blue- and white light-induced pupil constriction, retina-olivary pretectal nucleus, and retina- suprachiasmatic nuclei communication, light-induced c-Fos expression in the suprachiasmatic nuclei, and alterations in the locomotor activity daily rhythm. In addition, melatonin prevented the effect of glaucoma on melanopsin-expressing RGC mitochondrial alterations. These results support that melatonin protected the non-image-forming visual system against glaucoma, probably through a mitochondrial protective mechanism.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request. Some data may not be made available because of privacy or ethical restrictions.

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This research was supported by grants from the Agencia Nacional de Promoción Científica y Tecnológica [PICT 1563, PICT 2731], The University of Buenos Aires [20020100100678], and Consejo Nacional de Investigaciones Científicas y Técnicas [PIP 0707], Argentina. The funding organizations have no role in the design or conduct of this research.

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  1. Laboratory of Retinal Neurochemistry and Experimental Ophthalmology, Department of Human Biochemistry, School of Medicine/CEFyBO, University of Buenos Aires/CONICET, Paraguay 2155, 5P, (1121), Buenos Aires, Argentina

    María F. González Fleitas, Julián Devouassoux, Marcos L. Aranda, Hernán H. Dieguez, Juan S. Calanni, Agustina Iaquinandi, Pablo H. Sande, Damián Dorfman & Ruth E. Rosenstein

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  1. María F. González Fleitas
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María F González Fleitas: contributions to concept/design, acquisition of data, data analysis/interpretation; Julián Devouassoux: acquisition of data; Marcos L. Aranda: acquisition of data; Hernán H. Dieguez: acquisition of data; Juan S.Calanni: acquisition of data; Agustina Iaquinandi: acquisition of data; Pablo H. Sande: acquisition of data; Damian Dorfman: design/concept, interpretation/data analysis and manuscript drafting. Ruth E. Rosenstein: design/concept, interpretation/data analysis, manuscript drafting and article final approval.

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Correspondence to Ruth E. Rosenstein.

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González Fleitas, M.F., Devouassoux, J., Aranda, M.L. et al. Melatonin Prevents Non-image-Forming Visual System Alterations Induced by Experimental Glaucoma in Rats. Mol Neurobiol 58, 3653–3664 (2021). https://doi.org/10.1007/s12035-021-02374-1

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