Autophagy in cones

BioMed Radio - Washington University School of Medicine in St. Louis

The retina�s rods and cones allow us to see. But although scientists have an idea of what makes rods perform and flourish, they�ve been in the dark somewhat about what keeps cones working and thriving. Now, researchers at Washington University School of Medicine in St. Louis believe they�re closer to the answer and that their findings may one day help preserve vision in patients with age-related macular degeneration and other retinal diseases.

CELLS IN OUR EYES CALLED RODS AND CONES ALLOW US TO SEE. THE RODS ARE FOR DIM LIGHT, WHILE CONES ARE RESPONSIBLE FOR MOST OF WHAT WE THINK OF AS VISION, LIKE THE ABILITY TO SEE IN BRIGHT LIGHT AND TO SEE COLORS. NOW, A TEAM OF WASHINGTON UNIVERSITY RESEARCHERS HAS FOUND THAT A FORM OF CELLULAR RECYCLING IS NECESSARY FOR MAINTAINING CONE CELLS, AND THEY BELIEVE THE RECYLCING PATHWAY COULD PROVIDE A TARGET FOR TREATING SOME BLINDING RETINAL DISEASES. JIM DRYDEN HAS THE STORY�

ALTHOUGH CONE CELLS ONLY MAKE UP ONLY BETWEEN 1 AND 3 PERCENT OF OUR PHOTORECEPTORS, THEY�RE KEY TO COLOR VISION. WASHINGTON UNIVERSITY VISION RESEARCHER THOMAS FERGUSON SAYS THEY�RE REALLY RESPONSIBLE FOR MOST OF WHAT WE THINK OF AS VISION, AND THEY REQUIRE A LOT OF ENERGY.

(act) :15 o/c this function

It�s expensive, energywise. These cells need more and more
energy. As the lights get brighter, they need energy to
support all their metabolism, their functions of transducing
the vision signal and so forth. And they rely on autophagy
to support this function.

FERGUSON AND HIS COLLEAGUES STUDIED A CELLULAR PROCESS CALLED AUTOPHAGY IN CONE CELLS. AUTOPHAGY INVOLVES CELLS EATING PIECES OF THEMSELVES, EITHER TO GET RID OF BROKEN DOWN PARTS OF THE CELL OR TO SURVIVE UNDER STRESS.

(act) :20 o/c without stress

Autophagy functions in two ways: One is the stress-survival
pathway, but autophagy also functions at a baseline level.
Most cells have a little bit of it going on in the background.
You know, proteins get old. Organelles get old, and they have
to be removed, and this process removes them, sort of in the
background, without stress.

FERGUSON�S TEAM FOCUSED IN PARTICULAR ON AUTOPHAGY IN CONES, WHICH WAS DIFFICULT TO STUDY BECAUSE THE PERCENTAGE OF CONE CELLS IN THE RETINA IS PRETTY LOW. HIS LABORATORY STUDIED CONE CELLS IN MICE THAT WOULD ACTIVATE CERTAIN CHEMICALS WHEN AUTOPHAGY WAS ACTIVATED IN THE CONES.
(act) :14 o/v really interesting

Well, what we found, oddly, was that if we fasted mice for 24
hours, cones lit up with this reporting�it�s a GFP (a green
fluorescent protein). And only the cones did. That�s what was
really interesting.

SO NOT EATING FOR 24 HOURS SEEMED TO KICK START THE AUTOPHAGY PROCESS IN CONE CELLS. FERGUSON SAYS THAT�S PROBABLY BECAUSE WITHOUT FOOD, THERE IS LESS ENERGY FOR CONE CELLS TO USE, AND LIKE ALL NEURONS, CONE CELLS NEED A LOT OF ENERGY. SO HE THINKS AUTOPHAGY IS HELPING THE CELLS MEET THEIR NUTRITIONAL NEEDS. IN OTHER EXPERIMENTS, HE FOUND THAT THE AUTOPHAGY PROCESS ALSO WAS IMPORTANT WHEN CONE CELLS WERE EXPOSED TO BRIGHT LIGHT.

(act) :21 o/c intense light

Cones are very resistant to intense lighting. Well, what we found
was when we took out autophagy, the cones were no longer resistant
to intense light. And when you put them in bright light, the cones
died away. The second thing autophagy is doing � one, it�s resisting
starvation � the second thing it�s doing is resisting intense light.

BECAUSE AUTOPHAGY SEEMS SO IMPORTANT IN CONE FUNCTION, FERGUSON SAYS IT MIGHT BE POSSIBLE TO HELP TREAT SOME TYPES OF RETINAL DISEASE BY TRYING TO ACTIVATE THE AUTOPHAGY PATHWAY. IN THESE EXPERIMENTS, HIS TEAM DID THAT BY WITHHOLDING FOOD FROM MICE, BUT HE SAYS THAT SORT OF FASTING PROBABLY WOULDN�T BE REQUIRED TO LAUNCH THE PATHWAY IN PEOPLE.

(act) :10 o/c done chemically

So I�m not advocating starving people to save their vision. What
I�m advocating is, perhaps, stimulating this pathway to save their
vision, and that can be done chemically.

FERGUSON AND HIS TEAM REPORTED THEIR FINDINGS IN THE JOURNAL AUTOPHAGY. I�M JIM DRYDEN�

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