Sunday, October 23, 2011

Rabbit as an Animal Model for Eye Research

The main advantages to using rabbits as experimental models in eye research are the large size of the rabbit eye relative to its body and the several hundred years worth of accumulated data on the anatomy and physiology of the rabbit eye and its similarity to the human eye. Added to that, the fact that rabbits are easy to handle and breed and the most economical of the larger breed models, makes them ideal for ophthalmic research. [1]

The main avenues of eye research using the rabbit as a model are related to surgical interventions including cataract removal, intraocular lens insertion, corneal transplantation, laser refractive procedures, glaucoma shunt implantation, and intra-vitreal drug delivery. Strain selection is an important consideration for these experiments as the strain most commonly available is albino (New Zealand White [NZW]). Other strains are available that more closely approximate human ocular pigmentation (New Zealand/Dutch Belt or Dutch Belt) for experiments were pigmentation is important. Though there are no differences among male and female rabbits studied using these types of procedures, there are significant age-related differences. For example, young rabbits are commonly used because they have a more robust post-operative inflammatory response, which has been described as similar to that clinically observed in small children. [1]

Other areas of active biomedical research using the rabbit eye as a model include retinal detachment and proliferative vitreoretinopathy (PVR), retinoblastoma, and retinitis pigmentosa (RP). PVR is an abnormal wound healing process that takes place commonly after retinal detachment or other ocular trauma, resulting in a highly inflammatory environment within the eye. Treatment of PVR by vitrectomy or non-specific pharmacological prevention of cell proliferation are only marginally successful. Understanding intra-ocular inflammation is critical to developing new therapeutics for PVR and the rabbit PVR model will undoubtedly facilitate that effort. [2] A new model of retinoblastoma, created by injection of cultured human retinoblastoma cells into the sub-retinal space of immunosuppressed rabbits, displays intraocular tumors after one week that are remarkably similar to those observed in humans and that continue to grow for up to eight weeks. This model also has the advantage of developing viable vitreal tumor seeds when the retinal tumor is still only mid-sized. These vitreous seeds only develop very late in mouse models and are thought to be the cause of treatment failures in humans. This model presents the opportunity to test potential novel chemotherapeutics as well as delivery methods. [3] A new model of RP has been developed via creation of transgenic rabbits bearing a point mutation in the rhodopsin gene. The model has been characterized histologically and electrophysiologically and determined to display progressive retinal degeneration as a result of loss of rod function. While other animals currently serve as models for RP, this new rabbit model will offer additional options for testing therapeutic strategies including implantation of devices or prosthetics and local delivery of drugs or gene therapy. [4]

References
1. Gwon, A. (2008) The rabbit in cataract/IOL surgery. In: Tsonis, P.A. (ed.) Animal models in eye research. Elsevier, pp. 184-204.

2. Zahn, G. et al. (2010) Assessment of the integrin α5β1 antagonist JSM6427 in proliferative vitreoretinopathy using in vitro assays and rabbit model of retinal detachment. Invest. Ophthalmol. Vis. Sci. 51(2):1028-1035.

3. Kang, S.J. and Grossniklaus, H.E. (2011) Rabbit model of retinoblastoma. J. Biomed. Biotechnol. 2011:394730.

4. Kondo, M. et al. (2009) Generation of a transgenic rabbit model of retinal degeneration. Invest. Ophthalmol. Vis. Sci. 50(3):1371-1377.

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