Carmel Toomes

Retinal vasculopathies

Eye diseases are among the most common inherited human disorders, a reflection of the fact that mutations affecting visual function will rarely be lethal. This makes the study of inherited eye diseases a powerful tool for dissecting out the individual components of various developmental processes. With this aim in mind, our research focuses on identifying and characterising the proteins underlying retinal vasculogenesis and angiogenesis by studying inherited disorders of the retinal vascular system.

Our main research involves studying familial exudative vitreoretinopathy (FEVR), a disorder in which retinal vasculature development is prematurely halted resulting in visual defects and blindness due to retinal ischemia. Genetic studies have already identified three genes underlying FEVR and we are currently searching for at least three more. All three FEVR genes identified to date encode components of the Wnt signalling pathway, LRP5, FZD4 and NDP. We intend to investigate how these mutant proteins cause FEVR and to determine how they normally function in eye development. Through this work we hope not only to improve the treatment of people suffering from FEVR but also to shed light on more common blinding diseases involving blood vessel abnormalities such as retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration, the leading causes of blindness in the Western world.

Downey L, Bottomley H, Sheridan E, Ahmed M, Gilmour D, Inglehearn CF, Reddy A, Agrawal A, Bradbury J, Toomes C (2006). Reduced bone mineral density and hyaloid vasculature remnants in a consanguineous recessive FEVR family with a mutation in LRP5. Brit J Ophthalmol 90:1163-7.

Toomes C, Bottomley H, Jackson R, Town K, Scott S, Mackey D, Craig J, Jiang L, Yang Z, Zhang K, Trembath R, Woodruff G, Gregory-Evans C, Gregory-Evans K, Parker M, Black G, Markham A, Downey L and Inglehearn CF (2003). Mutations in LRP5 or FZD4 underlie the common FEVR locus on chromosome 11q13. Am J Hum Genet 74:721-730.

Danciger M, Hendrickson J, Lyon J, Toomes C, McHale JC, Fishman GA, Inglehearn CF, Jacobson SG and Farber DB (2001). CORD9 a new locus for arCRD: mapping to 8p11, estimation of frequency, evaluation of a candidate gene. Invest Ophthalmol Vis Sci 42:2458-2465.

Toomes C, James J, Wood AJ, Wu CL, McCormick D, Lench N, Hewitt C, Moynihan L, Roberts E, Woods CG, Markham A, Wong M, Widmer R, Ghaffar KA, Pemberton M, Hussein IR, Temtamy SA, Davies R, Read AP, Sloan P, Dixon MJ, Thakker NS (1999). Loss-of-function mutations in the cathepsin C gene result in periodontal disease and palmoplantar keratosis. Nature Genet 23:421-4.