Universität zu Köln

Liu, Hanhan, Bell, Katharina, Herrmann, Anja, Arnhold, Stefan, Mercieca, Karl, Anders, Fabian, Nagel-Wolfrum, Kerstin, Thanos, Solon and Prokosch, Verena (2022). Crystallins Play a Crucial Role in Glaucoma and Promote Neuronal Cell Survival in an In Vitro Model Through Modulating Muller Cell Secretion. Invest. Ophthalmol. Vis. Sci., 63 (8). ROCKVILLE: ASSOC RESEARCH VISION OPHTHALMOLOGY INC. ISSN 1552-5783

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Abstract

PURPOSE. The aim of this study was to explore the roles of crystallins in the context of aging in glaucoma and potential mechanisms of neuroprotection in an experimental animal model of glaucoma. METHODS. Intraocular pressure (IOP) was significantly elevated for 8 weeks in animals at different ages (10 days, 12 weeks, and 44 weeks) by episcleral vein cauterization. Retinal ganglion cells (RGCs) were quantified by anti-Brn3a immunohistochemical staining (IHC). Proteomics using ESI-LTQ Orbitrap XL-MS was used to analyze the presence and abundance of crystallin isoforms the retinal samples, respectively. Neuroprotective property and localization of three selected crystallins CRYAB, CRYBB2, and CRYGB as most significantly changed in retina and retinal layers were determined by IHC. Their expressions and endocytic uptakes into Muller cells were analyzed by IHC and Western blotting. Muller cell secretion of neurotrophic factors into the supernatant following CRYAB, CRYBB2, and CRYGB supplementation in vitro was measured via microarray. RESULTS. IOP elevation resulted in significant RGC loss in all age groups (P < 0.001). The loss increased with aging. Proteomics analysis revealed in parallel a significant decrease of crystallin abundance - especially CRYAB, CRYBB2, and CRYGB. Significant neuroprotective effects of CRYAB, CRYBB2, and CRYGB after addition to retinal cultures were demonstrated (P < 0.001). Endocytic uptake of CRYAB, CRYBB2, and CRYGB was seen in Muller cells with subsequent increased secretion of various neurotrophic factors into the supernatant, including nerve growth factor, clusterin, and matrix metallopeptidase 9. CONCLUSIONS. An age-dependent decrease in CRYAB, CRYBB2, and CRYGB abundance is found going along with increased RGC loss. Addition of CRYAB, CRYBB2, and CRYGB to culture protected RGCs in vitro. CRYAB, CRYBB2, and CRYGB were uptaken into Muller cells. Secretion of neurotrophic factors was increased as a potential mode of action.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Liu, Hanhan UNSPECIFIED UNSPECIFIED UNSPECIFIED Bell, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Herrmann, Anja UNSPECIFIED UNSPECIFIED UNSPECIFIED Arnhold, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Mercieca, Karl UNSPECIFIED UNSPECIFIED UNSPECIFIED Anders, Fabian UNSPECIFIED UNSPECIFIED UNSPECIFIED Nagel-Wolfrum, Kerstin UNSPECIFIED UNSPECIFIED UNSPECIFIED Thanos, Solon UNSPECIFIED UNSPECIFIED UNSPECIFIED Prokosch, Verena UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-686700
DOI:	10.1167/iovs.63.8.3
Journal or Publication Title:	Invest. Ophthalmol. Vis. Sci.
Volume:	63
Number:	8
Date:	2022
Publisher:	ASSOC RESEARCH VISION OPHTHALMOLOGY INC
Place of Publication:	ROCKVILLE
ISSN:	1552-5783
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language RETINAL GANGLION-CELLS; ENDOTHELIAL GROWTH-FACTOR; ALPHA-B-CRYSTALLIN; HEAT-SHOCK PROTEINS; EPITHELIUM-DERIVED FACTOR; OPTIC-NERVE; MATRIX METALLOPROTEINASES; NEUROTROPHIC FACTOR; CLUSTERIN EXPRESSION; MICROARRAY ANALYSIS Multiple languages Ophthalmology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68670