June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Comparison of complement pathway activation and synapse loss in young and aged mice undergoing light induced retinal degeneration
Author Affiliations & Notes
  • Sarah Warren Gooding
    Ophthalmology, Emory University, Atlanta, Georgia, United States
  • Micah A Chrenek
    Ophthalmology, Emory University, Atlanta, Georgia, United States
  • Jana Terrell Sellers
    Ophthalmology, Emory University, Atlanta, Georgia, United States
  • Jeffrey H Boatright
    Ophthalmology, Emory University, Atlanta, Georgia, United States
    Atlanta VAMC, Atlanta, Georgia, United States
  • Footnotes
    Commercial Relationships   Sarah Gooding, None; Micah Chrenek, None; Jana Sellers, None; Jeffrey Boatright, None
  • Footnotes
    Support  Research to Prevent Blindness, Abraham J. and Phyllis Katz Foundation, NIH R01 EY014026, NIH P30 EY006360, VA I21 RX001924
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 3594. doi:
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      Sarah Warren Gooding, Micah A Chrenek, Jana Terrell Sellers, Jeffrey H Boatright; Comparison of complement pathway activation and synapse loss in young and aged mice undergoing light induced retinal degeneration. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3594.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To determine whether aged versus young mice have increased synapse loss and inflammatory response to light-induced retinal degeneration (LIRD).

Methods : Young (61-62 days old) and aged (446-523 days old) Balb/c mice were exposed to four hours of 50 lux (dim), 2500 lux, 5000 lux, or 10,000 lux light and sacrificed two days later or seven days later following scotopic ERG. One eye was embedded in paraffin for immunohistochemistry. RNA was extracted from the retina of the other eye for use in digital droplet PCR to quantify gene expression. Whole eyes were sectioned and stained with antibodies against several components of complement pathways and against PSD95, a synapse marker. Images of C1q immunostained retina were threshholded and deposition scored to quantify C1q staining. Statistical testing was via two-way ANOVA with Tukey's post-hoc analysis.

Results : Retina function as measured by a- and b-wave amplitudes declined maximally in aged mice with 2500 lux light exposure whereas as 5000 lux or more was required to obtain maximal loss in young mice. C1qa gene expression was 50% greater in naïve aged versus young mice. CFH immunostaining and C1qa, C1qb, Cfh, Cfb, and C3 gene expression increased in both young and aged mice with LIRD. In contrast, C1Q immunostaining significantly increased only in the aged group two days following 10,000 lux light exposure (p≤0.0002). Aged mice exhibited less PSD95 immunostaining in the outer plexiform layer (OPL) seven days following 2500 or 5000 lux light exposure compared to young mice, even though young mice apparently lost more photoreceptor cell nuclei. PSD95 staining was nearly absent two days following 10,000 lux exposure in both age groups.

Conclusions : Aged mice lost retina function and OPL synapses at lower levels of light exposure, and had greater C1Q deposition in the ONL compared to young mice. It may be that, as in other CNS structures, aged mice have a hyper-inflammatory response to stressors that results in loss of synapses and associated function. These findings may have implications for retinal degenerative diseases whose etiologies include aging and inflammation.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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