Josh Varghese

Introduction. Retinitis Pigmentosa (RP) is progressive, degenerative disease that leads to the death of rod and cone photoreceptors. RP is one of the leading causes of blindness worldwide, especially in those who are in the 25-60 year old range.[i] The degeneration of the photoreceptors has been linked to activated retinal microglia through the mechanism of inflammatory cytokine production, ROS damage, and primary phagocytosis.[ii] These findings suggest that inhibiting the activation of microglial cells through the CX3CL1-CX3CR1 signaling pathway could be therapeutic. Methods. The rd10 mice model was utilized. PCR analyzed proinflammatory factor secretion by microglial cells.[iii] Fluorescence microscopy assessed the amount of ROS produced in the retina.[iv] Lastly, TUNEL staining analyzed the effect of upregulation of CX3CL1 on microglial induced apoptosis of photoreceptor cells.[v] Results. Rd10 mice displayed increase in expression of proinflammatory factors compared to the control mice.[vi] Fluorenscence microscopy revealed that rd10 mice had increased fluorescence in the outer retina, which signifies increased ROS.[vii]  Upregulation of CX3CL1 lead to decreased apoptosis of photoreceptor cells.[viii] Conclusion. Studies have shown that activation microglial cells leads to the pathogenesis of RP. Modulating the CX3CL1-CX3CR1 pathway has been shown to decrease the pathogenic effects and should be studied further to treat RP.

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2. Zabel MK, Zhao L, Zhang Y, et al. Microglial phagocytosis and activation underlying photoreceptor degeneration is regulated by CX3CL1-CX3CR1 signaling in a mouse model of retinitis pigmentosa. Glia. 2016;64(9):1479-1491.
3. Yoshida N, Ikeda Y, Notomi S, et al. Laboratory evidence of sustained chronic inflammatory reaction in retinitis pigmentosa. Ophthalmology. 2013;120(1):e5-e12.
4. Peng B, Xiao J, Wang K, So K, Tipoe GL, Lin B. Suppression of microglial activation is neuroprotective in a mouse model of human retinitis pigmentosa. J Neurosci. 2014;34(24):8139-8150.
5. Roche SL, Wyse-Jackson AC, Gómez-Vicente V, et al. Progesterone Attenuates Microglial-Driven Retinal Degeneration and Stimulates Protective Fractalkine-CX3CR1 Signaling. Hitchcock PF, ed. PLoS ONE. 2016;11(11):e0165197
6. Yoshida N, Ikeda Y, Notomi S, et al. Laboratory evidence of sustained chronic inflammatory reaction in retinitis pigmentosa. Ophthalmology. 2013;120(1):e5-e12.
7. Peng B, Xiao J, Wang K, So K, Tipoe GL, Lin B. Suppression of microglial activation is neuroprotective in a mouse model of human retinitis pigmentosa. J Neurosci. 2014;34(24):8139-8150
8. Roche SL, Wyse-Jackson AC, Gómez-Vicente V, et al. Progesterone Attenuates Microglial-Driven Retinal Degeneration and Stimulates Protective Fractalkine-CX3CR1 Signaling. Hitchcock PF, ed. PLoS ONE. 2016;11(11):e0165197