Timing scavenging to prevent age-related blindness

Light-detecting cells in the eye must renew their light-gathering apparatus each day at sunrise (for rod cells) or sunset (for cone cells) by shedding their outermost tips, which are then gobbled up and digested by surface (epithelial) cells. Nandrot and colleages now report in the December 20 issue of The Journal of Experimental Medicine that the epithelial cells need a protein called an integrin to detect when and how to gobble up the debris. Without it, the debris is taken up slowly but then accumulates to toxic levels inside the cell, eventually leading to blindness. An identical build-up of cellular debris is a hallmark of macular degeneration in humans, the most common cause of blindness in the elderly.

Shedding and debris collection must be precisely synchronized to maintain proper rod and cone cell function. How this synchronous cycle of uptake and digestion is maintained is not completely clear. Nandrot and colleagues now show that, in mice lacking the integrin, the normal burst of uptake activity at first light was completely missing and instead uptake occurred steadily throughout the day. Debris accumulated inside the cell and was not destroyed.

That epithelial cells could still take up debris at all was a surprise, as tissue culture experiments showed that cells missing this integrin were unable to pick up rod cell fragments. The link to digestion was also surprising because integrin signaling has never been linked to cellular digestion functions. Perhaps the same signal triggers a cascade that initiates both concerted uptake and digestion. The authors are now trying to identify the protein that binds to the integrin and triggers these functions.

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