A Link Be­tween Atheroscle­ro­sis and Mac­u­lar De­gen­er­a­tion?

Wellness Update - - Health Watch MD -

Anew study raises the in­trigu­ing pos­si­bil­ity that drugs pre­scribed to lower choles­terol may be ef­fec­tive against mac­u­lar de­gen­er­a­tion, a blind­ing eye dis­ease. Re­searchers at Wash­ing­ton Univer­sity School of Medicine in St. Louis have found that agere­lated mac­u­lar de­gen­er­a­tion, the lead­ing cause of vi­sion loss in Amer­i­cans over 50, shares a com­mon link with atheroscle­ro­sis. Both prob­lems have the same un­der­ly­ing de­fect: the in­abil­ity to re­move a buildup of fat and choles­terol. Be­neath the retina of a pa­tient with mac­u­lar de­gen­er­a­tion, the small light dots against the or­ange back­ground are choles­terol de­posits, and as choles­terol builds up, the area be­comes in­flamed, spurring the de­vel­op­ment of ab­nor­mal blood ves­sels that can lead to loss of vi­sion.

Work­ing in mice and in hu­man cells, the re­searchers shed new light on how de­posits of choles­terol con­trib­ute to mac­u­lar de­gen­er­a­tion and atheroscle­ro­sis and even blood ves­sel growth in some types of can­cer. Pa­tients who have atheroscle­ro­sis of­ten are pre­scribed med­i­ca­tions to lower choles­terol and keep ar­ter­ies clear. This study sug­gests that some of those same drugs could be eval­u­ated in pa­tients with mac­u­lar de­gen­er­a­tion. “Based on our find­ings, we need to in­ves­ti­gate whether vi­sion loss caused by mac­u­lar de­gen­er­a­tion could be pre­vented with choles­terol-low­er­ing eye drops or other med­i­ca­tions that might pre­vent the buildup of lipids be­neath the retina,” says se­nior in­ves­ti­ga­tor Ra­jen­dra S. Apte, MD, PhD. The new re­search cen­ters on macrophages, key im­mune cells that re­move choles­terol and fats from tis­sues. In mac­u­lar de­gen­er­a­tion, the ex­ces­sive buildup of choles­terol be­gins to oc­cur as we age, and our macrophages be­gin to mal­func­tion. In the “dry” form of age-re­lated mac­u­lar de­gen­er­a­tion, doc­tors ex­am­in­ing the eye can see lipid de­posits be­neath the retina. As those de­posits be­come larger and more nu­mer­ous, they slowly be­gin to de­stroy the cen­tral part of the eye, in­ter­fer­ing with the vi­sion needed to read a book or drive a car. As ag­ing macrophages clear fewer fat de­posits be­neath the retina, the macrophage cells them­selves can be­come bloated with choles­terol, cre­at­ing an in­flam­ma­tory process that leads to the for­ma­tion of new blood ves­sels that can cause fur­ther dam­age. Those ves­sels char­ac­ter­ize the later “wet” form of the dis­ease. “Ul­ti­mately, that in­flam­ma­tion cre­ates a toxic mix of things that leads to new blood ves­sel growth,” Apte ex­plains. “Most of the vi­sion loss from ‘wet’ mac­u­lar de­gen­er­a­tion is the re­sult of bleed­ing and scar-tis­sue for­ma­tion re­lated to ab­nor­mal ves­sel growth.” As part of their re­search, the sci­en­tists iden­ti­fied a pro­tein that macrophages need to clear fats and choles­terol. As mice and hu­mans age, they make less of the pro­tein, and macrophages be­come less ef­fec­tive at en­gulf­ing and re­mov­ing fat and choles­terol. Apte and his team found that macrophages, from old mice and in pa­tients with mac­u­lar de­gen­er­a­tion, have in­ad­e­quate lev­els of the pro­tein, called ABCA1, which trans­ports choles­terol out of cells. As a re­sult, the old macrophages ac­cu­mu­lated high lev­els of choles­terol and couldn’t in­hibit the growth of the dam­ag­ing blood ves­sels that char­ac­ter­ize the “wet” form of the dis­or­der. But when the re­searchers treated the macrophages with a sub­stance that helped restore lev­els of ABCA1, the cells could re­move choles­terol more ef­fec­tively, and the de­vel­op­ment of new blood ves­sels was slowed. “We were able to de­liver the drug, called an LXR ag­o­nist, in eye drops,” says first author Ab­doulaye Sene, PhD, a post-doc­toral fel­low in the Apte lab. “And we found that we could re­verse the mac­u­lar de­gen­er­a­tion in the eye of an old mouse. That’s ex­cit­ing be­cause if we could use eye drops to de­liver drugs that fight mac­u­lar de­gen­er­a­tion, we could fo­cus ther­apy only on the eyes, and we likely could limit the side ef­fects of drugs taken orally.” Sene and Apte also say that since macrophages are im­por­tant in atheroscle­ro­sis and in the for­ma­tion of new blood ves­sels around cer­tain types of can­cer­ous tu­mors, the same path­way also might pro­vide a tar­get for more ef­fec­tive ther­a­pies for those dis­eases. “We have shown that we can re­verse the dis­ease cas­cade in mice by im­prov­ing macrophage func­tion, ei­ther with eye drops or with sys­temic treat­ments,” Apte says. “Some of the ther­a­pies al­ready be­ing used to treat atheroscle­ro­sis tar­get this same path­way, so we may be able to mod­ify drugs that al­ready are avail­able and use them to de­liver treat­ment to the eye.” -This in­for­ma­tion pro­vided courtesy of Wash­ing­ton Univer­sity School of Medicine in St. Louis

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