Ocular genetics

Research programmes based around ocular genetics focus upon the investigation of genetic disorders associated with visual disability. The ultimate aims are to improve the diagnosis, management and treatment of such conditions.

Studies suggest that, in developed countries, between a third and a half of the diagnoses underlying childhood blind or partial-sighted registration are genetic, a figure that is likely to be an underestimate.

In many developing countries, where visual disability is significantly commoner, genetic conditions also represent an important group contributing to childhood blindness.

The 'genetic' conditions referred to in this context are monogenic, or Mendelian, conditions but of course many other common or complex disorders, such as age-related macular degeneration and cataract as well as primary open-angle glaucoma also have a substantial genetic contribution.

Research focus

Current work focuses on the characterisation of genes and proteins underlying:

  1. Inherited developmental disorders such as anophthalmia/microphthalmia and congenital cataract (Professor Graeme Black)
    Recently, we have demonstrated that X-linked microphthalmia and oculo-facial-cardio-dental syndrome are caused by mutation in an X-linked transcriptional regulator, BCOR, which encodes the BCL-6 transcriptional co-repressor.

    To study BCOR function, we have used morpholino oligonucleotides to knockdown expression of xtBcor in Xenopus tropicalis. This work demonstrated that xtBcor is required for lateral specification and suggests that BCOR is required in normal laterality determination in humans. Work now being undertaken examines how BCOR regulates PITX2C.
  2. Inherited retinal dystrophies (Professor Dorothy Trump and Dr Forbes Manson)
    Current projects include the identification of genes causing recessive retinal dystrophies as well, and inherited macular dystrophies such as Best disease and retinoschisis.

    Work to study genotype:phenotype correlations among mutations in BEST1 has demonstrated that BEST1 mutations also cause autosomal dominant vitreoretinochoroidopathy.

    Recently, we also demonstrated that a novel retinal phenotype, autosomal recessive bestrophinopathy, results from biallelic BEST1 mutation. Ongoing studies aim to elucidate the function of the normal protein.
  3. Molecular diagnosis of inherited retinal disease (Professor Graeme Black)
    Thanks to funding from both the Department of Health and The British Retinitis Pigmentosa Society, we now provide a diagnostic service for a range of inherited retinal dystrophies.