By Alexandra Scammell听
By determining how proteins in different areas of the eye鈥檚 lens change over time, researchers from Vanderbilt University鈥檚 School of Medicine Basic Sciences have learned more about how they could contribute to the mysterious progression of cataracts鈥攁 clouding of the lens that affects more than 65 million people worldwide each year.听听
鈥淭he risk of cataract onset increases as we age, so we want to know what causes that cataract to occur,鈥� said Lee Cantrell, doctoral candidate in the Chemical and Physical Biology Program and lead author of the , which was published in Molecular & Cellular Proteomics. He performed the work with Kevin Schey, professor of biochemistry, ophthalmology and visual sciences, and Romell Gletten, a recent graduate of the Department of Biochemistry.听
Cantrell likens the lens to a tree trunk: The center of the lens has fiber cells that were formed in utero and are as old as we are. But moving outward, progressively younger and younger fiber cells are found. With this concept in mind, the researchers obtained 16 healthy lenses and focused on three regions that correspond to relative developmental stages. 鈥淲e鈥檙e not looking at cataract formation necessarily, but we鈥檙e looking at 鈥� how the lens changes as it relates to age,鈥� Cantrell said. 鈥淲e鈥檙e not just looking at tissue aging, we鈥檙e looking at protein aging and what might happen within each region of the lens 鈥� over a lifetime.鈥�听
The researchers built on previous work that harnessed mass spectrometry, an analytical technique that measures the mass-to-charge ratio of molecules and is the conventional tool for doing proteomics鈥攖he study of proteins. Mass spectrometry measures more than one protein at a time and is quantitatively robust. They also employed an unconventional approach鈥攄ata-independent acquisition鈥攖hat allowed them to better identify scarce and difficult-to-measure molecular structures in the lens.听听
Because proteins degrade with age and become harder and harder to measure, using DIA is 鈥渟ignificantly more capable of measuring these low-abundance peptides and proteins,鈥� Cantrell said. 鈥淭hat鈥檚 what we鈥檙e doing here鈥攚e鈥檙e enhancing our capabilities with these next-generation techniques,鈥� he said.听
What Cantrell and the team found is that, generally, large changes in protein abundances occur once a person reaches age 50. 鈥淭here鈥檚 an approximate cutoff between younger-than-50 and older-than-50 lenses, where there鈥檚 a transition in the compositional abundance of all proteins,鈥� Cantrell said. For example, the team found that the protein SLC24A2鈥攁 calcium transporter鈥攕ignificantly modified with age.听
Although this research contributes to the understanding of lens changes with age and cataract formation, it is not yet known if these identified proteins are functional. According to Cantrell, there’s still the question of causality and correlation鈥攖his research does not answer that, he said.听
There鈥檚 鈥渁 long way to go鈥� until scientists can complete ideal in vitro (in a tube or dish) and in vivo (in living organisms) studies looking for therapeutics to target human cataract formation, Cantrell said, but 鈥渋t鈥檚 certainly in the long-term horizon.鈥澨�听
In the nearer future, this work lays a foundation for research into the functional significance of individual proteins, including low-abundance proteins like SLC24A2. Researchers can take a target like SLC24A2 and perturb a system to evaluate its function. This research is 鈥渙pening up new chapters and entirely new research projects,鈥� Cantrell said.听