ARVO LIVE: Using mitochondria, senolytic agents to treat retinal injury

Ram Kannan, PhD, FARVO, principal investigator and adjunct professor of Ophthalmology at David Geffen School of Medicine, UCLA, Doheny Eye Institute, made a pair of presentations at the Association for Research in Vision and Ophthalmology annual meeting in New Orleans. He offers some of the highlights in a conversation with Ophthalmology Times.

Video transcript

Editor’s note: Transcript lightly edited for clarity.

Ram Kannan, PhD, FARVO:

I do two presentations at this meeting. One is on two topics that are of most interest in our lab. One is about mitochondria, and the function and how retinal injury can be blocked by mitochondrial peptides. That was the first one.

We had a second one, which is on an emerging field called senescence, how cells get senescent and how senescence contributes to AMD. So these are the two.

So in the first one, what, what we presented was to show how some endogenous mitochondrial peptides can block experimental retinal injury in models of smoking. So we use smoking as the model here to cause retinal injury and mitochondrial dysfunction. We showed how a peptide from endogenous mitochondria is protected. Under these conditions, we did it with multiple methods, like studying mitochondrial function, particularly mitochondrial respiration, biogenesis, the all the metabolism of mitochondria. So, this is just to show how important mitochondria is for retinal function. That was the first one.

The second one and that is going to be the emerging field of senescence. Now, recently, it has been shown that senescence plays an important role as a risk factor for AMD. So, we took genetic models of AMD dysfunction and we showed that inducing senescence can aggravate the injury and how peptides that are perfused to the nanoparticles can prevent such sort of information.

So, this is a field that is going to grow rapidly, because now, the research is on how senolytic agents that block senescence in animal models. We have also done it in human tissues, where we are shown that there is RP senescence, both in the RP as well as the rest of the retina. So it is important to find a therapy using either mitochondrial endogenous agents or externally with other peptides with which we have a lot of experience. So we showed for the first time using cigarette smoke extract, that RP cells get injured up to one week or so. and how giving these peptides encapsulated in nanoparticles can be very effective in promoting that. In other words, all our work is based on how we can develop strategies for preventing AMD in the human situation.