July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Fighting inflammation to save cones: anti-inflammatory approaches to slow down cone death in a mouse model of Retinitis Pigmentosa
Author Affiliations & Notes
  • Martina Biagioni
    National Research Council (CNR), Neuroscience Institute, Pisa, Italy
    Regional Doctorate School of Neuroscience,University of Florence, Florence, Italy
  • Viviana Guadagni
    Department of Biology, University of Pisa, Pisa, Italy
  • Elena Novelli
    National Research Council (CNR), Neuroscience Institute, Pisa, Italy
  • Enrica Strettoi
    National Research Council (CNR), Neuroscience Institute, Pisa, Italy
  • Footnotes
    Commercial Relationships   Martina Biagioni, None; Viviana Guadagni, None; Elena Novelli, None; Enrica Strettoi, None
  • Footnotes
    Support  Fondazione Roma, Italy; Vision Research Foundation, USA
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 4601. doi:
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      Martina Biagioni, Viviana Guadagni, Elena Novelli, Enrica Strettoi; Fighting inflammation to save cones: anti-inflammatory approaches to slow down cone death in a mouse model of Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4601.

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

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Purpose : In Retinitis Pigmentosa (RP) a genetic defect causes the degeneration of rods, followed by the secondary loss of cones. The biological mechanism leading to demise of cones remains elusive. We previously shown that in rd10 mutant mice, a model of human RP, the peak of cone death, P45, is associated with retinal overexpression of inflammatory genes, including Ccl2 Il6 and Il1-beta. Resident microglia and infiltrating monocytes are believed to produce these species, contributing to the development of adverse milieu. Following the hypothesis that an anti-inflammatory treatment could slow down cone death, we implemented a protocol of steroid administration over the time window of maximum rod and cone death.

Methods : Groups of rd10 mice received daily 4mg/kg Dexamethasone (DEXA)(Soldesam forte, 4mg/ml) administered sub-cutaneously, from P23 to P45 or to P60. Control mice received water. For histological studies, retinas harvested at P45 or P60 were fixed in 4% PFA, stained with antibodies to label rods, cones and microglial cells and examined with a Leica SP2 confocal microscope or with a Zeiss Axio ImagerZ2 ApoTome2 fluorescence microscope. The number of cones and microglial cells/retina was estimated counting on whole mount retinas after Cone Opsin or Iba1 antibody staining, respectively. Visual acuity was tested at P45 and P60 with a Prusky water maze.

Results : We found an increase of 32% in the number of surviving cones in DEXA treated mice compared to matched controls at P45; Iba1 staining showed strong microglial activation and infiltration in the outer retina. DEXA treatment lowered of 37% the number of microglial cells in the outer retina.
Similarly, the retina of DEXA treated mice retained 28% more cones at P60 compared to matched controls. Microglia activation again mirrored closely the pattern of cone death.
Prusky water maze tests shown a significantly higher visual acuity in DEXA treated than in control mice both at P45 and P60.

Conclusions : Although the role of inflammation in RP is becoming evident, anti-inflammatory pharmacological approaches specifically aiming at rescuing cones in this disease have never been tested. Our findings suggest a causal link between local inflammatory response and worsening of cone fate, opening the perspective of slowing down retinal decay by using steroids; these drugs are already widely employed in clinical ophthalmology.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.


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