Antonia Angulo

Gradual morphogenesis of retinal neurons in the peripheral retinal margin of adult monkeys and humans

The adult mammalian retina has for long been considered to lack a neurogenerative capacity. However, retinal stem/progenitor cells, which can originate retinal neurons in vitro, have been recently reported in the ciliary body of adult mammals. Here we explored the possibility of retinal neurogenesis occurring in vivo in adult monkeys and humans. We found the presence of cells expressing molecular markers of neural and retinal progenitors in the nonlaminated retinal margin and ciliary body pars plana of mature primates. By means of immunohistochemistry and electron microscopy we also observed photoreceptors and other retinal cell types in different stages of morphological differentiation along the peripheral retinal margin. These findings allow us to extend to primates the idea of neurogenesis aimed at retinal cell turnover throughout life. J. Comp. Neurol. 511:557–580, 2008.

Morphological Impairments in Retinal Neurons of the Scotopic Visual Pathway in a Monkey Model of Parkinson's Disease

Physiological abnormalities resulting from death of dopaminergic neurons of the central nervous system in Parkinsons disease also extend to the retina, resulting in impaired visual functions. In both parkinsonian patients and animal models, low levels of dopamine and loss of dopaminergic cells in the retina have been reported. However, the morphology and connectivity of their postsynaptic neurons, the amacrine cells, have not been analyzed. Here we report, with macaques chronically treated with 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) as a model of Parkinsons disease, that morphological impairments in dopaminergic retinal neurons and their plexus in the inner retina are accompanied by an immunoreactivity decrease in γ‐aminobutyric acidergic and glycinergic amacrine cells. Especially deteriorated were AII amacrine cells, the main neuronal subtype postsynaptic to dopaminergic cells, which exhibited a marked loss of lobular appendages and dendritic processes. Concomitantly, electrical synapses among AII cells, as well as chemical synapses between these and rod bipolar cells, were highly deteriorated in parkinsonian monkeys. These results highlight that the scotopic visual pathway is severely impaired in the parkinsonian condition and provide a morphological basis for a number of abnormalities found in electrophysiological and psychophysical trials in Parkinsons disease patients and animal models. J. Comp. Neurol. 493:261–273, 2005.

A reliable method for Golgi staining of retina and brain slices

Although the classical Golgi method is a powerful means for structural analysis of the brain, it is generally considered to be an unpredictable technique making anatomists wary of using it. Often, even when successful staining has occurred, deposits of silver chromate crystals on the surface of the tissue obscure examination. This paper describes a simple procedure for Golgi impregnation of retina and brain slices so that good, even staining is obtained and crystal formation is avoided. The most outstanding feature of the method is the consistency of results. This consistency is due to two factors: (1) the accurate determination of the optimal chromation by measuring the rise of pH in the solutions and (2) the uniform penetration of dichromate and silver nitrate to the specimen by using a freely hanging, sandwiching technique. We suggest that the method described here can be applied to other parts of the nervous system and will be a reliable way to identify and better classify new cell types.

Natural Compounds from Saffron and Bear Bile Prevent Vision Loss and Retinal Degeneration.

All retinal disorders, regardless of their aetiology, involve the activation of oxidative stress and apoptosis pathways. The administration of neuroprotective factors is crucial in all phases of the pathology, even when vision has been completely lost. The retina is one of the most susceptible tissues to reactive oxygen species damage. On the other hand, proper development and functioning of the retina requires a precise balance between the processes of proliferation, differentiation and programmed cell death. The life-or-death decision seems to be the result of a complex balance between pro- and anti-apoptotic signals. It has been recently shown the efficacy of natural products to slow retinal degenerative process through different pathways. In this review, we assess the neuroprotective effect of two compounds used in the ancient pharmacopoeia. On one hand, it has been demonstrated that administration of the saffron constituent safranal to P23H rats, an animal model of retinitis pigmentosa, preserves photoreceptor morphology and number, the capillary network and the visual response. On the other hand, it has been shown that systemic administration of tauroursodeoxycholic acid (TUDCA), the major component of bear bile, to P23H rats preserves cone and rod structure and function, together with their contact with postsynaptic neurons. The neuroprotective effects of safranal and TUDCA make these compounds potentially useful for therapeutic applications in retinal degenerative diseases.