An Acute Injury Model for the Phenotypic Characteristics of Geographic Atrophy

Imran A. Bhutto, Shuntaro Ogura, Rajkumar Baldeosingh, D. Scott McLeod, Gerard A. Lutty, Malia M. Edwards

Research output: Contribution to journalArticle

Abstract

Purpose: Geographic atrophy (GA) is the late stage of non-neovascular age-related macular degeneration. A lack of animal models for GA has hampered treatment efforts. Presented herein is a rat model for GA using subretinal injection of sodium iodate (NaIO3). Methods: Rats were given subretinal injections of NaIO3 (5 μg/μL) using a pico-injector. Fundus photographs and spectral domain optical coherent tomography scans were collected at 1, 3, 7, 14, and 28 days after injection, at which time rats were euthanized and eyes were enucleated. Eyes were either cryopreserved or dissected into retinal and choroidal flatmounts. Fluorescence immunohistochemistry was performed for retinal glial fibrillary acidic protein (activated Müller cells and astrocytes) and vimentin (Müller cells), as well as peanut agglutin lectin (photoreceptors) labeling. RPE/choroids were labeled for RPE65 and CD34. Images were collected on Zeiss confocal microscopes. Results: Fundus photos, spectral domain optical coherent tomography, and RPE65 staining revealed well-demarcated areas with focal loss of RPE and photoreceptors in NaIO3-treated rats. At 1 day after injection, RPE cells appeared normal. By 3 days, there was patchy RPE and photoreceptor loss in the injected area. RPE and photoreceptors were completely degenerated in the injected area by 7 days. A large subretinal glial membrane occupied the degenerated area. Choriocapillaris was highly attenuated in the injected area at 14 and 28 days. Conclusions: The rat model reported herein mimics the photoreceptor cell loss, RPE atrophy, glial membrane formation, and choriocapillaris degeneration seen in GA. This model will be valuable for developing and testing drugs and progenitor cell regenerative therapies for GA.

Original languageEnglish (US)
Pages (from-to)AMD143-AMD151
JournalInvestigative ophthalmology & visual science
Volume59
Issue number4
DOIs
StatePublished - Mar 20 2018

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Geographic Atrophy
Optical Tomography
Wounds and Injuries
Injections
Neuroglia
Peanut Agglutinin
Photoreceptor Cells
Membranes
Choroid
Glial Fibrillary Acidic Protein
Macular Degeneration
Vimentin
Cell- and Tissue-Based Therapy
Astrocytes
Atrophy
Stem Cells
Animal Models
Fluorescence
Immunohistochemistry
Staining and Labeling

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

An Acute Injury Model for the Phenotypic Characteristics of Geographic Atrophy. / Bhutto, Imran A.; Ogura, Shuntaro; Baldeosingh, Rajkumar; McLeod, D. Scott; Lutty, Gerard A.; Edwards, Malia M.

In: Investigative ophthalmology & visual science, Vol. 59, No. 4, 20.03.2018, p. AMD143-AMD151.

Research output: Contribution to journalArticle

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abstract = "Purpose: Geographic atrophy (GA) is the late stage of non-neovascular age-related macular degeneration. A lack of animal models for GA has hampered treatment efforts. Presented herein is a rat model for GA using subretinal injection of sodium iodate (NaIO3). Methods: Rats were given subretinal injections of NaIO3 (5 μg/μL) using a pico-injector. Fundus photographs and spectral domain optical coherent tomography scans were collected at 1, 3, 7, 14, and 28 days after injection, at which time rats were euthanized and eyes were enucleated. Eyes were either cryopreserved or dissected into retinal and choroidal flatmounts. Fluorescence immunohistochemistry was performed for retinal glial fibrillary acidic protein (activated M{\"u}ller cells and astrocytes) and vimentin (M{\"u}ller cells), as well as peanut agglutin lectin (photoreceptors) labeling. RPE/choroids were labeled for RPE65 and CD34. Images were collected on Zeiss confocal microscopes. Results: Fundus photos, spectral domain optical coherent tomography, and RPE65 staining revealed well-demarcated areas with focal loss of RPE and photoreceptors in NaIO3-treated rats. At 1 day after injection, RPE cells appeared normal. By 3 days, there was patchy RPE and photoreceptor loss in the injected area. RPE and photoreceptors were completely degenerated in the injected area by 7 days. A large subretinal glial membrane occupied the degenerated area. Choriocapillaris was highly attenuated in the injected area at 14 and 28 days. Conclusions: The rat model reported herein mimics the photoreceptor cell loss, RPE atrophy, glial membrane formation, and choriocapillaris degeneration seen in GA. This model will be valuable for developing and testing drugs and progenitor cell regenerative therapies for GA.",
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