» Articles » PMID: 32025182

Potential Effects of Progranulin and Granulins Against Retinal Photoreceptor Cell Degeneration

Overview
Journal Mol Vis
Date 2020 Feb 7
PMID 32025182
Citations 2
Authors
Affiliations
Soon will be listed here.
Abstract

Purpose: The authors previously reported that progranulin attenuated retinal degeneration. The present study focused on the role of progranulin and its cleavage products, granulins, in the pathogenesis of photoreceptor degeneration.

Methods: Photoreceptor degeneration was induced with excessive exposure of murine photoreceptor cells and the retinas of albino mice to white fluorescent light. Damaged photoreceptor cells and retinas were examined using a cell death assay, western blotting, and immunostaining.

Results: Even after proteolytic cleavage, treatment with progranulin or its cleavage products or both exerted protective effects on photoreceptors against light exposure. In the murine retina, the expression levels of granulins and the macrophage and microglia marker Iba-1 were increased at 48 h after light exposure. Additionally, progranulin and Iba-1 double-positive cells had accumulated in the outer nuclear layer, the primary location of photoreceptor cells.

Conclusions: These results suggest that progranulin or its cleavage products, granulins, or both may be therapeutic targets for age-related macular degeneration and other neurodegenerative diseases.

Citing Articles

Retinal Degeneration and Microglial Dynamics in Mature Progranulin-Deficient Mice.

Takahashi K, Nakamura S, Shimazawa M, Hara H Int J Mol Sci. 2021; 22(21).

PMID: 34768987 PMC: 8584076. DOI: 10.3390/ijms222111557.


Lysosomal Dysfunction and Other Pathomechanisms in FTLD: Evidence from Progranulin Genetics and Biology.

Zhou X, Kukar T, Rademakers R Adv Exp Med Biol. 2021; 1281:219-242.

PMID: 33433878 PMC: 8672701. DOI: 10.1007/978-3-030-51140-1_14.

References
1.
L Petkau T, Neal S, Orban P, MacDonald J, Hill A, Lu G . Progranulin expression in the developing and adult murine brain. J Comp Neurol. 2010; 518(19):3931-47. DOI: 10.1002/cne.22430. View

2.
Egashira Y, Suzuki Y, Azuma Y, Takagi T, Mishiro K, Sugitani S . The growth factor progranulin attenuates neuronal injury induced by cerebral ischemia-reperfusion through the suppression of neutrophil recruitment. J Neuroinflammation. 2013; 10:105. PMC: 3765381. DOI: 10.1186/1742-2094-10-105. View

3.
Kuse Y, Tsuruma K, Sugitani S, Izawa H, Ohno Y, Shimazawa M . Progranulin promotes the retinal precursor cell proliferation and the photoreceptor differentiation in the mouse retina. Sci Rep. 2016; 6:23811. PMC: 4814875. DOI: 10.1038/srep23811. View

4.
Laird A, Van Hoecke A, De Muynck L, Timmers M, Van Den Bosch L, Van Damme P . Progranulin is neurotrophic in vivo and protects against a mutant TDP-43 induced axonopathy. PLoS One. 2010; 5(10):e13368. PMC: 2954192. DOI: 10.1371/journal.pone.0013368. View

5.
Kuse Y, Tsuruma K, Mizoguchi T, Shimazawa M, Hara H . Progranulin deficiency causes the retinal ganglion cell loss during development. Sci Rep. 2017; 7(1):1679. PMC: 5431873. DOI: 10.1038/s41598-017-01933-8. View