Real-time imaging of single nerve cell apoptosis in retinal neurodegeneration

doi:10.1073/pnas.0405479101

Real-time imaging of single nerve cell apoptosis in retinal neurodegeneration

^*Department of Pathology and Glaucoma and Optic Nerve Head Research Group, and Departments of ^‡Visual Sciences and ^§Cell Biology, Institute of Ophthalmology, University College London, Bath Street, London EC1V 9EL, United Kingdom

Communicated by Alfred Sommer, Johns Hopkins University, Baltimore, MD, July 28, 2004 (received for review June 1, 2004)

Abstract

Apoptotic nerve cell death is implicated in the pathogenesis of several devastating neurodegenerative conditions, including glaucoma and Alzheimer's and Parkinson's diseases. We have devised a noninvasive real-time imaging technique using confocal laser-scanning ophthalmoscopy to visualize single nerve cell apoptosis in vivo, which allows longitudinal study of disease processes that has not previously been possible. Our method utilizes the unique optical properties of the eye, which allow direct microscopic observation of nerve cells in the retina. We have been able to image changes occurring in nerve cell apoptosis over hours, days, and months and show that effects depend on the magnitude of the initial apoptotic inducer in several models of neurodegenerative disease in rat and primate. This technology enables the direct observation of single nerve cell apoptosis in experimental neurodegeneration, providing the opportunity for detailed investigation of fundamental disease mechanisms and the evaluation of interventions with potential clinical applications, together with the possibility of taking this method through to patients.

Footnotes

↵ † To whom correspondence should be addressed. E-mail: m.cordeiro{at}ucl.ac.uk.
Abbreviations: cLSO, confocal laser scanning ophthalmoscope; DiAsp, (4-(4-(didecylamino) styryl)-N-methylpyridinium iodide); IOP, intraocular pressure; OHT, ocular hypertension; RGC, retinal ganglion cell; SSP, staurosporine.