Purchase this article with an account.
Pedro Lax, Agustina Noailles, Laura Campello, Oksana Kutsyr, Victoria Maneu, Nicolás Cuenca; Lipopolysaccharide Induced Microglial Activation Exacerbates Retinal Degeneration in Animal Models of Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5382.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Activated microglia has been associated with neurodegenerative diseases, where it can exert beneficial or detrimental effects depending on the pathophysiological context. The objective of this work was to study the effect of lipopolysaccharide (LPS)-induced activation of retinal microglia on the progression of morphological and functional alterations associated with retinal neurodegeneration.
Twelve homozygous P23H-3 and twelve wild-type Sprague-Dawley rats were injected twice weekly with LPS (60 µg/Kg, i.p.) or vehicle (PBS) from P20 to P60. Electroretinograms, flow cytometry and vertical retinal cryostat sections were used to evaluate the morphological and functional state of the retinal tissue.
LPS administration to control SD rats did not induce significant changes in the function or morphology of the retina. However, in P23H rats LPS administration increased the activation of microglia, evidenced by a significant increase (ANOVA, Bonferroni’s test, P<0.05) in the expression of MHCII and CD45 antigens in CD11b-positive cells detected by flow cytometry analysis. Moreover, immunohistochemistry assays revealed that in P60 LPS-treated P23H rats microglial cells were located not only in the plexiform layers of the retina, but also in both the inner and outer nuclear layers. LPS-induced microglial activation in P23H rats was accompanied by a greater deterioration in the a- and b-wave amplitudes (34% lower in both cases; ANOVA, Bonferroni’s test, P<0.05 and P<0.001, respectively), a higher loss of photoreceptor (3 to 4 photoreceptor rows less; ANOVA, Bonferroni’s test, P<0.001) and a worsening of synaptic connectivity, as compared to vehicle-administered P23H rats.
Chronic administration of LPS exacerbates microglial activation and accelerates photoreceptor cell death and retinal dysfunction in retinitis pigmentosa.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
This PDF is available to Subscribers Only