Sci. Aging Knowl. Environ., 22 December 2004
Vol. 2004, Issue 51, p. nf115
[DOI: 10.1126/sageke.2004.51.nf115]


Trashing Vision

Cell receptor helps prevent garbage pileups in the eye

Mitch Leslie

Put your garbage out when it's not trash day, and the waste will sit at the curb. A similar problem with rubbish collection in the eye might underlie some age-related types of blindness, according to new work. Shackling a receptor that controls cells' stickiness disrupts the normal junk-pickup schedule, the study shows. The results might help researchers better understand diseases in which cellular refuse blemishes the retina.

Light damages the sensitive pigments in the retina of the eye, so each day cells there renew themselves by replacing their sun-scarred tips, which contain the burned-out pigments. Rods, which help animals see in dim light, dump these segments in the morning. Adjacent cells called retinal pigment epithelium (RPE) cells digest the junk as it detaches, and when cleanup falters, trouble ensues. For example, deposits mar the retina in age-related macular degeneration (AMD), a leading cause of blindness in the elderly. Researchers don't understand how cells control trash collection, but previous work in rodents showed that removing a surface receptor on RPE cells called MerTK stalls the process and leads to blindness. Cell biologist Silvia Finnemann of Cornell's Weill Medical College in New York City and colleagues wanted to probe the role of another receptor, known as {alpha}v{beta}5, that helps determine whether cells stick together and allows RPE cells to grab worn-out segments.

Animals genetically altered to lack {alpha}v{beta}5 gradually went blind, the researchers found. Furthermore, numerous gobs of pigment resembling those that amass in AMD and other eye disorders appeared in their retinas. In the test tube, RPE cells from the engineered mice couldn't absorb as much junk as cells from normal animals could. Those results suggest that {alpha}v{beta}5 spurs RPE cells to gulp retinal flotsam. The team sampled eye tissue at different times of the day and measured how much refuse the cells had swallowed. In control rodents, the amount spiked in the morning, but in altered rodents, it changed little. Previous studies indicated that {alpha}v{beta}5 turns on proteins such as MerTK, so the researchers measured the amount of phosphate-tagged MerTK, the active form. Quantities surged in the morning in control animals but stayed small in the altered mice. The findings suggest that hampering {alpha}v{beta}5 throws off the trash-collection schedule. Rodents without MerTK go blind quickly, but those lacking {alpha}v{beta}5 lose their eyesight gradually, indicating that they can clear up some of the noxious garbage, says Finnemann. Keeping vision clear depends not only on whether cells can absorb retinal junk but also on when they absorb it, she says.

"It's a very important piece of work," says cell biologist Roy Silverstein of the Cleveland Clinic in Ohio. It sheds light on the mechanisms that control whether RPE cells ingest garbage, and the findings might apply to other scavenging cells in the body, which also tote {alpha}v{beta}5 and MerTK, he says. Future research should delve further into the communication system that allows cells to schedule garbage collection, he adds. This work might clarify how RPE cells know when it's time to pick up the trash.

December 22, 2004
  1. E. F. Nandrot et al., Loss of synchronized retinal phagocytosis and age-related blindness in mice lacking {alpha}v{beta}5 integrin. J. Exp. Med., 13 December 2004 [e-pub ahead of print] doi:10.1084/jem.20041447[Abstract/Free Full Text]
Citation: M. Leslie, Trashing Vision. Sci. Aging Knowl. Environ. 2004 (51), nf115 (2004).

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