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Momoko Kobayashi, Emi Nakajima, Thomas R Shearer, Mitsuyoshi Azuma; Accumulation of a calpain specific α-spectrin breakdown product in drusen from AMD patients: Possible calpain activation in RPE and photoreceptors. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3059. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
An important role of retinal pigment epithelial cells (RPE) is phagocytosis of shedding photoreceptor outer segments. In aged-related macular degeneration (AMD), RPE and photoreceptor cells degenerate and lead to progressive vision loss. The amorphous drusen deposits found between the RPE and Bruch’s membrane are early bio-markers for AMD. Drusen contain dysfunctional components derived from the RPE. Analysis of drusen may thus allow tracking of the early biochemical changes. Photoreceptor and RPE cells cultured under hypoxia, show activation of calpains, proteolysis of substrates (e.g., α-spectrin), and cell death. Activation of calpains following hypoxia may thus cause proteolysis/degeneration. No direct evidence has as yet demonstrated activation of calpains in AMD. The purpose of this study was to measure the calpain-specific 150 kDa breakdown product from α-spectrin (SBDP150kDa) in drusen from human AMD patients.
Human eyes were obtained from the Lions Vision Gift, using informed consent. Five μm, formalin-fixed paraffin sections were subjected to immunohistochemistry for SBDP150kDa, a marker for calpain activation.
Typical drusen were found in the sections from some of the dry or wet AMD patients. Significant staining for SBDP150kDa was observed only in drusen from AMD patients. Normal and retinitis pigmentosa (RP) patients with no drusen did not stain for SBDP150kDa.
A specific marker of calpain activation, SBDP150kDa, was detected for the first time in drusen from AMD patients. This suggests that calpain-induced proteolysis participates in the degradation of photoreceptor and/or RPE cells in AMD.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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