June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Acute Photoreceptor Ablation Results in Loss of Horizontal Cells but Preservation of Bipolar Cells in the Primate Macula
Author Affiliations & Notes
  • Teresa Puthussery
    Herbert Wertheim School of Optometry & Vision Science, University of California Berkeley, Berkeley, California, United States
    Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, California, United States
  • Jacqueline Gayet
    Herbert Wertheim School of Optometry & Vision Science, University of California Berkeley, Berkeley, California, United States
  • Kristel Cosio
    Herbert Wertheim School of Optometry & Vision Science, University of California Berkeley, Berkeley, California, United States
  • Hector C Baez
    Center for Visual Science, University of Rochester, Rochester, New York, United States
    Department of Biomedical Engineering, University of Rochester, Rochester, New York, United States
  • Karteek Kunala
    Center for Visual Science, University of Rochester, Rochester, New York, United States
  • Juliette E McGregor
    Flaum Eye Institute, Department of Ophthalmology, University of Rochester, Rochester, New York, United States
    Center for Visual Science, University of Rochester, Rochester, New York, United States
  • Footnotes
    Commercial Relationships   Teresa Puthussery None; Jacqueline Gayet None; Kristel Cosio None; Hector Baez None; Karteek Kunala None; Juliette McGregor None
  • Footnotes
    Support  Research reported in this publication was supported by the NEI/NIH under Award No. P30EY001319, P30EY003176 and U24EY033275. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This study was supported by an Unrestricted Grant to the University of Rochester Department of Ophthalmology from Research to Prevent Blindness, NY, NY and a Steven E Feldon Scholarship from the Flaum Eye Institute to JEM.
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 3804. doi:
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      Teresa Puthussery, Jacqueline Gayet, Kristel Cosio, Hector C Baez, Karteek Kunala, Juliette E McGregor; Acute Photoreceptor Ablation Results in Loss of Horizontal Cells but Preservation of Bipolar Cells in the Primate Macula. Invest. Ophthalmol. Vis. Sci. 2023;64(8):3804.

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

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Abstract

Purpose : The success of cell-based therapies for photoreceptor degenerations depends on transplanted photoreceptors forming synaptic connections with the host retina. Although the impact of photoreceptor loss on the inner retina has been well-characterized in lower mammals, the impact on the cone-dominated primate macula is not well understood. Here, we used a laser ablation model of acute photoreceptor degeneration to determine the impact of deafferentation on the survival and synaptic integrity of inner retinal neurons.

Methods : We studied 4 laser lesions from 3 adult macaque eyes (2 M. fascicularis, 8-15 years, 1 M. Mulatta 19 years). To create focal regions of photoreceptor ablation, we used a femtosecond-pulsed laser (730 nm, 27-33 J/cm2) focused on the photoreceptor layer using an adaptive optics scanning light ophthalmoscope. Lesions were made ~1-15 degrees from the foveal center and eyes were harvested for histology at 3 weeks, 4, 8 & 12 months post-ablation. The integrity of horizontal cells (HCs) and different bipolar cell types (BCs) was assessed using cell-type specific and synaptic markers. Deafferented regions were identified with antibodies for VGLUT1. Cell densities were compared between lesioned and neighboring unlesioned regions by one-sample t-test.

Results : Deafferentation was associated with focal loss of H1 and H2 HCs as early as 3 weeks post-ablation (p<0.0001). This result was confirmed with three HC markers (ONECUT1, PVALB, CALB1), suggesting neuronal loss rather than down-regulation of marker proteins. In contrast, the densities of rod BC (PKCα, p = 0.52), On-BCs (Islet 1, p =0.19) and Off midget BCs (recoverin, p=0.23) were unchanged at all timepoints. Deafferented On-BCs showed marked loss of dendritic mGluR6 and TRPM1 as early as 3 weeks post-lesion but expression of somatic TRPM1 remained (n = 3 lesions, 2 retinas). In the central fovea, the observed changes in post-receptoral neurons were laterally offset from the laser lesions consistent with deafferentation, rather than direct laser damage, underlying the changes.

Conclusions : Acute photoreceptor ablation in primate leads to loss of HCs and On-BC-associated synaptic proteins as early as 3 weeks post-deafferentation. The long-term survival of rod and cone BCs in lesioned regions holds promise for cell-based therapies.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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