Home > Research at NEI > Pediatric, Developmental and Genetic Ophthalmology

Pediatric, Developmental and Genetic Ophthalmology

Current Research

Uveal coloboma is a potentially blinding, developmental abnormality of the eye caused by failure of the optic fissure to close during the 5th week of human gestation. The purpose of our clinical and basic research is to better understand the genetic and developmental mechanisms of optic fissure closure. Our short-term goal is to provide better diagnostics and genetic counseling for our patients; our long-term goal is to find preventions and/or treatments for this condition. Our approach is summarized in the following figure:

Genes for Uveal Coloboma chart.

Our clinical studies are focused on understanding how patients with coloboma see and what, if any, associated clinical conditions they might have. Using state-of-the-art diagnostic equipment, we are trying to better understand the anatomy of eyes and the visual pathways of patients with coloboma. We are also collecting detailed clinical and epidemiology information.

Using the tools of modern genetics, we are also searching for genes important in optic fissure closure in humans. We use mouse and zebrafish models to better understand how genes are regulated during the course of optic fissure closure. Specific mutant mouse strains are also being investigated to discover genes that might cause coloboma in humans. Thse studies have identified that two zinc finger proteins, Nlz1 and Nlz2, regulate optic fissure closure through a Pax2-dependent mechanism. We are currently trying to understand the developmental role of these and other genes from our screen in the normal process of optic fissure closure and to search for causative mutations in humans.


Name Title E-Mail
Brian Brooks, MD
PubMed Author Search
Pediatric Ophthalmologist brooksb@nei.nih.gov
Yuri Sergeev Staff Scientist sergeevy@nei.nih.gov
Delphine Blain, MS, MBA Genetic Counselor db417p@nih.gov
Amy Turiff Genetic Counselor turiffa@nei.nih.gov
Prasad Alur, Ph.D. Lab Manager ra215u@nih.gov
Sanita Bharti, Ph.D Postdoctoral Research Fellow sanitab@nei.nih.gov
Elangovan Boobalan, Ph.D. Research Associate elangovanb@mail.nih.gov
Monika Dolinska Research Associate dolinskam@nei.nih.gov
Sunit Dutta, Ph.D. Postdoctoral Resarch Fellow sunit.dutta@nih.gov
Felix Onojafe, D.V.M. Senior Lab Technician onojafef@mail.nih.gov
Casey Hadsall, RN, MSN Nurse Coordinator hadsallc@nei.nih.gov
Jennifer Sarchet Nurse Coordinator sarchetj@nei.nih.gov
Shahila Sriskanda IRTA Student shahila.sriskanda@nih.gov

Recent Publications

  • Nichols L, Alur RP, Boobalan E, Caruso RC, Stone EM, Swaroop A, Johnson MA, Brooks BP. Molecular characterization of two novel CRX mutations causing autosomal dominant Leber congenital amaurosis. Human Mutation. 31:E1472-83 (2010)
  • Alur RP, Camasamudram V, Brown JD, Mehtani M, Onojafe IF, Sergeev YV, Boobalan E, Jone MP, Tang K, Liu H, Chun-hong X, Gong X, Brooks BP. Papillorenal syndrome-causing missense mutations in PAX2/Pax2 result in hypomorphic alleles in mouse and human. PloS Genet 6(3):e1000870. Doi 10.1371/journal.pgen.100870. (2010)
  • Salchow DJ, Kohlhase J, Miller M, Kadon N, FitzGibbon EJ, Caruso RC, Brooks BP. Absent optic chiasm presenting with horizontal nystagmus. J Pediatr Ophthalmol Strabismus. 47: 187-91 (2010)
  • Solomon BD, Pineda-Alvarez DE, Balog JZ, Hadley D, Gropman AL, Nandagopal R, Han JC, Hahn JS, Blain D, Brooks B, Muenke M. Compound heterozygosity for mutations in PAX6 in a patient with complex brain anomaly, neonatal diabetes mellitus, and microphthalmia. Am J Med Genet. 149A:2543-6 (2009)
  • Brown JD, Duuta S, Bharti K, Bonner RF, Munson PJ, Dawid IB, Akhtar AL, Onojafe IF, Alur RP, Gross JM, Hejtmancik JF, Jiao X, Chan WY, Brooks BP. Expression profiling during ocular development identifies two Nlz genes with a critical role in optic fissure closure. Proc Natl Acad Sci U S A. 106:1462-7 (2009).
  • Asai-Coakwell M, French CR, Ye M, Garcha K, Bigot K, Perena AG, Staehling-Hamptom K, Mema S, Chanda B, Mushegian A, Bamforth S, Doschak MR, Li G, Dobbs MB, Giampietro PF, Brooks BP, Vijayalakshmi P, Sauvei Y, Abitbol M, Sundaresan P, van Heyningen V, Pourquie O, Underhill TM, Waskiewicz AJ, Lehmann OJ. Incomplete penetrance and phenotypic variability characterize Gdf6-attributable oculo-skeletal phenotype. Hum Molec Genetics. 15:1110-21 (2009)
  • Meredith M, Gordon L, Clauss S, Sachdev V, Smith A, Perry M, Brewer C, Zalewski C, Kim J, Solomon B, Brooks BP, Gerber L, Turner M, Domingo D, Hart TC, Graf J, Reynolds J, Gropman A, Yanovski J, Collins F, Nabel E, Cannon R, Gahl W, Introne W. Comprehensive evaluation of patients with Hutchinson-Gilford progeria syndrome. NEJM. 358:592-604 (2008).
  • Brooks BP, Larson DM, Chan CC, Kjellstron S, Smith RS, Crawford MA, Lamoreux L, Huizing M, Hess R, Jiao X, Hejtmancik FJ, Maminishkis A, John SWM, Bush R, Pavan WJ. Analysis of ocular hypopigmentation in Rab38cht/cht mice. Inv Ophthal Vis Sci. 48:3905-13 (2007).