Towards maximising information extraction from rodent models of ocular disease.

B M Davis,M F Cordeiro,L Langley,E M Normando,J Brenton,L Guo

doi:10.1038/cddis.2016.174

B M Davis, M F Cordeiro + Show 4 more

Open Access

https://doi.org/10.1038/cddis.2016.174

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Abstract

Loss of retinal ganglion cells (RGCs) has a central role in retinal disorders including glaucoma, which result in progressive vision loss over time. The global glaucoma prevalence is currently estimated to be 3.54% of the population aged between 40 and 80 years.1 Currently, raised intraocular pressure (IOP) presents the only modifiable risk factor. However, some glaucoma patients continue to lose vision despite having well controlled IOPs.2 This has led to a search for alternative strategies to promote RGC preservation.3 Experimental glaucoma models and whole-retinal mounts have proven a useful ex vivo tool for the assessment of potential new treatments using well-established protocols for labelling RGCs, including using nuclear-restricted transcription factor brain-specific homeobox/POU domain protein 3A (Brn-3A).

Highlights

Animal models of ocular disease have made an invaluable contribution to the development of new therapies, dramatically enhancing the quality of life of people with sight-threatening diseases.[4]
retinal ganglion cells (RGCs) quantification from brain-specific homeobox/POU domain protein 3A (Brn-3A)-labelled retinal whole mounts is frequently achieved by sampling regions for manual counting
This technique provides an improvement on assessing RGC health from histological cross-sections, it remains susceptible to error, both from inter- and intra-operator variability and variation of RGC density across a retina

Summary

Introduction

Animal models of ocular disease have made an invaluable contribution to the development of new therapies, dramatically enhancing the quality of life of people with sight-threatening diseases.[4]. The development of automated whole-retinal measures of RGC density has sought to overcome limitations of the sampling approach, typically reducing each whole-retinal mount into a single mean RGC density data point.[8] As typical healthy adult rat retina contains between 80 000 and 100 000 RGCs, a large amount of potentially useful information is discarded by only reporting changes as a single mean RGC density.

Results

Conclusion