Apoptosis not only culprit in cell death

New Orleans-Apoptosis may be the best characterized form of programmed cell death-but it isn’t in isolation, said Joan W. Miller, MD.

Alternative pathways are also at work, said Dr. Miller, chief and chairwoman, Department of Ophthalmology, Massachusetts Eye and Ear, Boston.   

Past research has focused on the mechanisms of cell death in the hopes of identifying therapeutic targets in degenerative retinal disease.

Previously, Dr. Miller said, apoptosis was thought to be the main mechanism of photoreceptor degeneration, but research shows it is not.

“Indeed, the caspase enzymes-which play a central role for inducing apoptosis-are activated in dying photoreceptor cells in experimental modes,” Dr. Miller said. “Paradoxically, inhibiting caspases doesn’t sufficiently protect against cell loss.”

Dr. Miller pointed out the involvement of other cell death mechanisms-specifically mentioning accumulating evidence demonstrating nonapoptotic forms of cell death, such as autophagy and necrosis, which are also regulated by specific molecular machinery, such as autophangy-related proteins and receptor-interacting protein RIP kinases, respectively.

“Certainly there are different pathogenesis,” she said. “There are different pathways, redundant and complimentary, for all these different diseases and some are overlapping.”

The key point, she said, is a research focus on combination therapy in order to achieve neuroprotection. By identifying alternative cell death pathways and understanding how to inhibit them, we can prevent vision loss in multiple eye disorders.

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