Staring into the Eyes of Death—Measuring Apoptosis One Neuron at a Time
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Neuronal apoptosis, or programmed cell death, underlies many neurodegenerative diseases, including Alzheimer and Parkinson disease. If scientists could measure and track this phenomenon, they could obtain priceless information about neurodegenerative pathology. So far, measuring apoptosis in vivo has proven quite difficult, even for clumps of cells, but how about doing it one neuron at a time? In this week’s early online edition of PNAS, researchers from University College London report that they have done just that.
Frederick Fitzke and colleagues have capitalized on the transparent nature of the mammalian eye to visualize apoptosis in real time. Using a prototype confocal laser scanning ophthalmoscope, first author Francesca Cordeiro and colleagues obtained images of dying rat and primate retinal neurons. The researchers had labeled the retinas with a fluorescent protein, annexin 5, which only binds to cells undergoing apoptosis.
Cordeiro and colleagues tested the system in various models of retinal degeneration. When they examined rats with ocular hypertension, for example, they found that peak apoptosis occurred about three to four weeks after the onset of glaucoma. The beauty of the system is that the microscope allows annexin 5 to be resolved at the cellular level, so that the authors could track individual neurons as they bound more annexin 5 and got brighter, and then the researchers could watch them eventually fade as apoptosis ran its deadly course.
“Our technique opens up the possibility for the investigation of nerve cell apoptosis in the same animal over a period of hours, days, weeks, or even longer,” write the authors. They also emphasize how useful the method will be to examine how external factors, such as the environment or therapeutics, may influence the course of apoptosis. While the most obvious application is in the study of retinal degeneration, neurodegeneration in the eye can serve as a model for degeneration in other parts of the brain (read, for example, how some drugs can slow huntingtin-mediated degeneration in fruit fly compound eyes; see ARF related news story).—Tom Fagan
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Primary Papers
- Cordeiro MF, Guo L, Luong V, Harding G, Wang W, Jones HE, Moss SE, Sillito AM, Fitzke FW. Real-time imaging of single nerve cell apoptosis in retinal neurodegeneration. Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13352-6. PubMed.
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Comments
King Edward Medical University Lahore, Pakistan
This is a good effort, and I think that it would be important in the field of retinal disease. It is clear that the retinal and hippocampal neurons are much different. Being sensitive to light, the retinal neurons have different physiological levels. Retinal neurons are loaded with vitamin A, and the areas degenerated in Alzheimer's disease are found to be deficient in this. On the other hand, it is difficult to study a neuron, with its physiological relations and functions, in vivo. So it is important to investigate the progression of pathways of neuronal degeneration. This goal is supported by the present research material. I think that NOS-3 (nitric oxide synthase 3) has a prominent role during apoptotic development in AD. This needs to be studied. The present article could be much more helpful for the patients of retinal detachment.
References:
de la Monte SM, Chiche J, von dem Bussche A, Sanyal S, Lahousse SA, Janssens SP, Bloch KD. Nitric oxide synthase-3 overexpression causes apoptosis and impairs neuronal mitochondrial function: relevance to Alzheimer's-type neurodegeneration. Lab Invest. 2003 Feb;83(2):287-98. PubMed.
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