Investigative Ophthalmology & Visual Science Cover Image for Volume 65, Issue 7
June 2024
Volume 65, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2024
Removal of Bmal1 disrupts mitochondrial ultrastructure in mouse cone photoreceptors
Author Affiliations & Notes
  • nicolas diaz
    Pharmacology and toxicology & Neuroscience Institute, Morehouse School of Medicine, Atlanta, Georgia, United States
  • Sondip Biswas
    Pharmacology and toxicology & Neuroscience Institute, Morehouse School of Medicine, Atlanta, Georgia, United States
  • Khaleel Bashir
    Pharmacology and toxicology & Neuroscience Institute, Morehouse School of Medicine, Atlanta, Georgia, United States
  • Gianluca Tosini
    Pharmacology and toxicology & Neuroscience Institute, Morehouse School of Medicine, Atlanta, Georgia, United States
  • Kenkichi Baba
    Pharmacology and toxicology & Neuroscience Institute, Morehouse School of Medicine, Atlanta, Georgia, United States
  • Footnotes
    Commercial Relationships   nicolas diaz None; Sondip Biswas None; Khaleel Bashir None; Gianluca Tosini None; Kenkichi Baba None
  • Footnotes
    Support  NIH grants: GM135112-01A1 (NIGMS) to K.B, R21-EY031821 (NEI) to G.T.
Investigative Ophthalmology & Visual Science June 2024, Vol.65, 2549. doi:
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      nicolas diaz, Sondip Biswas, Khaleel Bashir, Gianluca Tosini, Kenkichi Baba; Removal of Bmal1 disrupts mitochondrial ultrastructure in mouse cone photoreceptors. Invest. Ophthalmol. Vis. Sci. 2024;65(7):2549.

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

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Abstract

Purpose : The mammalian retina contains an autonomous circadian system that is implicated in the regulation of several functions. Previous studies have shown that removal of the clock gene Bmal1 from the mouse retina affects retinal circuitry, cone photoreceptor’s spectral identity, and cones viability during aging. We have also shown that removal of Bmal1 from 661W cells, a cone like cell line, altered mitochondria inner-membrane formation, and reduced the level of Mitofilin, a protein implicated in regulation of mitochondria architecture. In the present study, we investigated the effect of Bmal1 removal on the mitochondria of the mouse cone photoreceptors.

Methods : Retinal Bmal1 knock-out (rBKO) and the appropriate age-matched control were used in the experiments. Mitochondrial morphology was investigated in mouse retina using transmission electron microscopy (JEOL JEM-1400). The number, size, and shape of mitochondria in cone inner segment (CIS) and cone pedicles (CP) were analyzed using ImageJ (NIH) software. The level of Mitofilin in the cone cells was determined by immunostaining with Mitofilin and Arrestin4 antibodies. Intensity of Mitofilin signal was calculated relative to Arrestin4 signals.

Results : Our results showed the number and size of mitochondria did not differ in CIS between control and rBKO retinas, but the number mitochondria increased, and mitochondria size decreased in the CP of rBKO retinas. The number of degenerated mitochondria was significantly increased in both CIS and CP in rBKO retina and variations of mitochondrial cristae width were also affected in both CIS and CP of rBKO with respect to what observed in the controls. Immunostaining of Mitofilin revealed a significant reduction (about 20%) in the level of Mitofilin in the cones of rBKO relative to what observed in cones obtained from control retina.

Conclusions : Our results confirm our previous observation obtained in 661W cells and indicate that removal of Bmal1 affected the mitochondria structure also in the mouse cones. Interestingly, it seems that the disruption is more prominent in CPs than CISs thus suggesting that removal of Bmal1 may also be implicated in the regulation of cones synapse. Finally, our studies suggest that Bmal1 plays an important role in mitochondria biology.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

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