June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Role of microglia in the survival of allogeneic neonatal retina transplanted into subretinal space
Author Affiliations & Notes
  • Minali Prasad
    Department of Ophthalmology, Boston University School of Medicine, Boston, Massachusetts, United States
  • Reza A Badian
    Oslo University Hospital, Norway
  • Ambika Manhapra
    Department of Ophthalmology, Boston University School of Medicine, Boston, Massachusetts, United States
  • Lee Tirrell
    Northeastern University, Massachusetts, United States
  • Kin-Sang Cho
    Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Andrew W Taylor
    Department of Ophthalmology, Boston University School of Medicine, Boston, Massachusetts, United States
  • Tat Fong Ng
    Department of Ophthalmology, Boston University School of Medicine, Boston, Massachusetts, United States
  • Sharmila Masli
    Department of Ophthalmology, Boston University School of Medicine, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Minali Prasad None; Reza A Badian None; Ambika Manhapra None; Lee Tirrell None; Kin-Sang Cho None; Andrew Taylor None; Tat Fong Ng None; Sharmila Masli None
  • Footnotes
    Support  Massachusetts Lions Eye Research Fund
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 4612. doi:
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      Minali Prasad, Reza A Badian, Ambika Manhapra, Lee Tirrell, Kin-Sang Cho, Andrew W Taylor, Tat Fong Ng, Sharmila Masli; Role of microglia in the survival of allogeneic neonatal retina transplanted into subretinal space. Invest. Ophthalmol. Vis. Sci. 2023;64(8):4612.

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

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Abstract

Purpose : Resident microglia can present retinal autoantigens to initiate inflammation. Previous studies have shown light-induced migration of resident retinal microglia to subretinal space (SRS) with their density directly proportional to the light intensity. The objective was to determine whether microglia in the SRS cause an early rejection of neonatal retina (NNR) and to assess graft integrity under different light conditions.

Methods : Recipient mice (BALB/c) raised in dark until 8 weeks of age were exposed to 500 lux (Bright, BL) or 100 lux (Dim, DL) light intensities for 2 weeks to induce higher or lower densities of migrated microglia in the SRS relative to those exposed to 250 lux (Conventional, CL). Allogeneic NNR (C57Bl/6) collected on postnatal day 0 were transplanted into the SRS of recipients maintained under post-transplant light conditions similar to or different from donors. Grafts harvested (allogeneic on day 35 and syngeneic grafts on day 35 or 56) were subjected to morphologic scoring with respect to area, perimeter, and axial length. Delayed type hypersensitivity (DTH) response was determined in allogeneic NNR recipients by measuring the change in ear thickness after ear-challenge with irradiated C57BL/6 spleen cells.

Results : The study included 33 allogeneic and 8 syngeneic NNR transplants. Graft survival in the allogeneic BL(pre-transplant)/DL(post-transplant) group (n=8) was 75%. However, none of the allogeneic grafts in BL/BL or DL/BL group survived. Morphological score of grafts in BL/DL group (9.22) was comparable to that of syngeneic grafts at day 35 (9.89). Score for grafts in allogeneic DL/DL and CL/CL group were relatively higher (14.61 and 11.00 respectively). Significantly increased ear thickness compared to negative controls (indicative of DTH response) was detectable only in BL/BL group (p<0.01).

Conclusions : BL-induced high microglia density in the recipient subretinal space has a detrimental effect on retinal graft survival regardless of the microglia density in the graft. The loss of allogeneic graft in BL-exposed recipients corresponds with the emergence of an allogeneic DTH response. Relatively lower microglia densities in recipients exposed to DL or CL correspond with improved graft survival and morphology. This suggests that resident retinal microglia contribute to an immune response against an allogeneic retinal transplant, presumably by presenting alloantigens.

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

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