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Forschungsinstitut fuer Augenheilkunde
INSTITUTE FOR OPHTHALMIC RESEARCH
FORSCHUNGSINSTITUT FÜR AUGENHEILKUNDE

Support from the German Ophthalmological Society (DOG)

Young Researcher of the Institute for Ophthalmic Research (IoR) supported by 5000 € from the German Ophthalmological Society (DOG) for the submission of a DFG grant (German Research Council)

DFG Project Summary

Inherited neurodegenerative diseases of the retina are mainly triggered by primary genetic defects in rod photoreceptors, causing first rod- and then secondarily mutation-independent cone-loss. While the loss of rods has only minor consequences for human vision, and indeed often goes unnoticed in patients, secondary loss of cones causes devastating blindness. Therefore, stopping secondary cone death has the potential to preserve useful vision in patients suffering from genetically different types of retinal dystrophies. Additionally, as primary rod degeneration is associated with high genetic heterogeneity, cone preservation enables bypassing time-consuming determination of initial genetic defect. However, knowledge of the degenerative mechanisms underlying cone cell death remains scarce. We have previously shown that both primary rod and cone degeneration is governed by non-apoptotic mechanisms, such as increased enzymatic activities of calpains, poly-ADP-ribose-polymerase (PARP), and histone deacetylases (HDAC) (Sancho-Pelluz et al. 2008;Trifunovic et al. 2010.) Inhibition of aforementioned enzymatic activities bears high potential for novel neuroprotective therapies for photoreceptor degeneration, as it has been previously shown for rod degeneration.
In the future we plan to investigate mechanisms of secondary mutation-independent cone degeneration in retinal degeneration1 (rd1) mouse model using in vitro, ex vivo and in vivo techniques hoping to pinpoint novel neuroprotective targets for secondary cone degeneration.

To be able to perform this research I have applied for a Principal Investigator Grant to German Research Foundation (DFG). This project proposal was awarded a financial support from German Ophthalmologic Association (DOG) aimed at promoting a high level research in Ophthalmology in Germany.

Selected publications:

  1. Trifunović D, Sahaboglu A, Kaur J, Mencl S, Zrenner E, Ueffing M, Arango-Gonzalez B, Paquet-Durand F (2012). Neuroprotective Strategies for the Treatment of Inherited Photoreceptor Degeneration. Current Molecular Medicine, 12:598-612 (Review).
  2. Paquet-Durand F, Beck S, Michalakis S, Goldmann T, Huber G, Mühlfriedel R, Trifunović D, Fischer MD, Fahl E, Duetsch G, Becirovic E, Wolfrum U, van Veen T, Biel M, Tanimoto N, Seeliger MW (2011). A key role for cyclic nucleotide gated (CNG) channels in cGMP-related retinitis pigmentosa. Human Molecular Genetics, 20(5):941-7.
  3. Trifunović D, Dengler K, Michalakis S, Zrenner E, Wissinger B, Paquet-Durand F (2010). cGMP-Dependent Cone Photoreceptor Degeneration in the cpfl1 Mouse Retina. The Journal of Comparative Neurology, 518(17):3604-17.
  4. Trifunović D, Karali M, Camposampiero D, Ponzin D, Banfi S, Marigo V (2008). A high-resolution RNA expression atlas of Retinitis Pigmentosa genes in the human and mouse retinas. Investigative Ophthalmology and Visual Science, 49(6):2330-6.