rd1 Mouse Retina Shows an Imbalance in the Activity of Cysteine Protease Cathepsins and Their Endogenous Inhibitor Cystatin C
Abstract
PURPOSE: To compare in vivo levels, spatial localization, and in vitro secretion of cysteine protease cathepsins and cystatin C (cysC) in the retinal degeneration 1 (rd1) mouse model of retinitis pigmentosa and control (wt) mouse retinas. METHODS: The spatial localization, protein contents, cysC levels and cathepsin-B, -S, and -L activities in wt and rd1 retinas at postnatal (PN) days 2, 7, 14, 21, and 28 were analyzed by immunostaining, spectrophotometry, ELISA, and fluorescence spectrophotometry. The in vitro secretion of cysC and cysteine proteases by PN7 retinal explants into the conditioned medium (RCM) was quantified. RESULTS: The pigment epithelium, photoreceptors, and inner retinal and ganglion cell layers of both wt and rd1 retinas showed cysC and cathepsin-B labeling. CysC immunostaining was extensive in the optic nerve head fibers. The rd1 explants secreted higher amounts of cysteine protease into the RCM. The protein content in wt and rd1 retinal extracts increased up to PN14, then decreased in rd1 but not in wt. In rd1 extracts at PN14 to -28, cathepsin activity was higher and increased with age, but the cysC level was higher and constant. The ratios of cathepsin activity to cysC (cathepsin-L at PN2 and total, -B, and -L at PN14 to -28) were higher in rd1 extracts. CONCLUSIONS: Similar localization of both cathepsin-B and cysC in wt and rd1 retinas along with lower proteins and higher cathepsin activity in rd1 retinal extracts and RCM are consistent with their localization in extracellular matrix and a role in physiopathologic remodeling in wt and rd1 retinas.
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Cathepsin B is identified in mouse, bovine, and human RPE, with some variation in protein expression at least in RPE from individual rats.
“Cathepsin B has also been identified in the mouse (Alizadeh et al., 2006; Ahuja et al., 2008), bovine (Fröhlich and Klessen, 2001), and human (Hoppe et al., 2004b) RPE, although there appears to be some variation in the level of protein expression, at least in RPE from individual rats (Wassélius et al., 2003).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Ahuja et al., 2008
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The cell biology of the retinal pigment epithelium
Lakkaraju, A., Umapathy, A., Tan, L. X., Daniele, L., Philp, N. J., Boesze-Battaglia, K., & Williams, D. S. (2020) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2020.100846 · Cited by 422 · see citing works
- Authors
- Ahuja, S., Ahuja-Jensen, P., Johnson, L. E., Caffe´, A. R., Abrahamson, M., Ekstro¨m, P. A. R., & van Veen, T.
- Affiliations
- From the Department of Ophthalmology Research, Biomedical Centre B-13, and the
- Skåne University Hospital (SE)
- ORCID
- Abrahamson, Magnus
- Venue
- Investigative Opthalmology & Visual Science
- Published
- 2008-03-01
- Volume
- 49
- Issue
- 3
- Pages
- 1089
- ISSN
- 0146-0404 (ISSN-L)
- 1552-5783
- OpenAlex
- W2119601216
- Cited by
- 18
- References
- 47
- Citations by year
- 2022: 1 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 2 · 2016: 1 · 2015: 2 · 2014: 2 · 2013: 1 · 2012: 1
- FWCI
- 0.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Investigative Ophthalmology & Visual Science (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Keywords
- rd1 mouse, retinitis pigmentosa, cysteine protease, cathepsin B, cathepsin S, cathepsin L, cystatin C, retinal degeneration, protease-inhibitor balance, extracellular matrix remodeling, retinal pigment epithelium, photoreceptors, ganglion cell layer, optic nerve head
- MeSH terms
- Animals, Animals, Newborn, Cathepsins, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Mice, Inbred C3H, Mice, Mutant Strains, Organ Culture Techniques, Protease Inhibitors, Retina, Retinitis Pigmentosa, Spectrometry, Fluorescence, Cystatins, Culture Media, Conditioned, Fluorescent Antibody Technique, Indirect, Mice, Cystatin C
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