Retinal ganglion cell loss and gliosis in the retinofugal projection following intravitreal exposure to amyloid-beta.
Neurobiol Dis
; 147: 105146, 2021 01.
Article
en En
| MEDLINE
| ID: mdl-33122075
ABSTRACT
Pathological accumulations of amyloid-beta (Aß) peptide are found in retina early in Alzheimer's disease, yet its effects on retinal neuronal structure remain unknown. To investigate this, we injected fibrillized Aß1-42 protein into the eye of adult C57BL/6 J mice and analyzed the retina, optic nerve (ON), and the superior colliculus (SC), the primary retinal target in mice. We found that retinal Aß exposure stimulated microglial activation and retinal ganglion cell (RGC) loss as early as 1-week post-injection. Pathology was not limited to the retina, but propagated into other areas of the central nervous system. Microgliosis spread throughout the retinal projection (retina, ON, and SC), with multiplex protein quantitation demonstrating an increase in endogenously produced Aß in the ON and SC corresponding to the injected retinas. Surprisingly, this pathology spread to the opposite side, with unilateral Aß eye injections driving increased Aß levels, neuroinflammation, and RGC death in the opposite, un-injected retinal projection. As Aß-mediated microglial activation has been shown to propagate Aß pathology, we also investigated the role of the Aß-binding microglial scavenger receptor CD36 in this pathology. Transgenic mice lacking the CD36 receptor were resistant to Aß-induced inflammation and RGC death up to 2 weeks following exposure. These results indicate that Aß pathology drives regional neuropathology in the retina and does not remain isolated to the affected eye, but spreads throughout the nervous system. Further, CD36 may serve as a promising target to prevent Aß-mediated inflammatory damage.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Células Ganglionares de la Retina
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Precursor de Proteína beta-Amiloide
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Gliosis
Límite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Neurobiol Dis
Asunto de la revista:
NEUROLOGIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos