Ontogenetic Cell Death and Phagocytosis in the Visual System of Vertebrates

Abstract

Programmed cell death (PCD), together with cell proliferation, cell migration, and cell differentiation, is an essential process during development of the vertebrate nervous system. The visual system has been an excellent model on which to investigate the mechanisms involved in ontogenetic cell death. Several phases of PCD have been reported to occur during visual system ontogeny. During these phases, comparative analyses demonstrate that dying cells show similar but not identical spatiotemporally restricted patterns in different vertebrates. Additionally, the chronotopographical coincidence of PCD with the entry of specialized phagocytes in some regions of the developing vertebrate visual system suggests that factors released from degenerating cells are involved in the cell migration of macrophages and microglial cells. Contradicting this hypothesis however, in many cases the cell corpses generated during degeneration are rapidly phagocytosed by neighboring cells, such as neuroepithelial cells or M€ uller cells. In this review, we describe the occurrence and the sites of PCD during the morphogenesis and differentiation of the retina and optic pathways of different vertebrates, and discuss the possible relationship between PCD and phagocytes during ontogeny.

Identification of functional networks associated with cell death in the retina of OXYS rats during the development of retinopathy

“…Apoptosis is the main mechanism of cellular homeostasis during the development of the retina: this process ensures the selection and elimination of extraneous neurons, reduces their number down to the physiological norm, promotes adequate neurogenesis, and ensures formation of well-defined neurons and selection of appropriate interneuronal connections. 23,24 Disturbances in the signaling pathway of cell death at the early stages of development contribute to the onset of various diseases related to loss of vision (such as retinal dystrophy and retinopathy of prematurity). 25 It is possible that the changes in the regulation of retinal apoptosis-that we uncovered here during the period of completion of retinal development in the early ontogenesis-contribute to the development of AMD-like retinopathy in OXYS rats by the age of 3 months.…”

Early development of the nervous system of the eutherian <i>Tupaia belangeri</i>

“…tween macrophages and apoptotic cells could be demonstrated in the catshark (Bejarano-Escobar et al, 2013). For these and other reasons, Francisco-Morcillo et al (2014) conclude that, in the developing visual system, "dying cells show similar but not identical spatiotemporally restricted patterns in different vertebrates". The same appears to hold true for macrophages, which may or may not contribute to the elimination of apoptotic cells.…”

Müller glia and phagocytosis of cell debris in retinal tissue

“…The phagocytic role of M€ uller glia becomes relevant in degenerative regions where microglial cells are absent. Different phases of PCD have been described during retinal development (for reviews, see Valenciano et al 2009;Francisco-Morcillo et al 2014). During these phases, there has been observed occasional spatiotemporal coincidence of dying cells with macrophages and microglial precursors in the developing avian retina (Cuadros et al 1991), and in both the embryonic and postnatal mammalian retina (Hume et al 1983;Ashwell et al 1989;Egensperger et al 1996;Rodr ıguez-Gallardo et al 2005;Santos et al 2008;Bejarano-Escobar et al 2011), suggesting that cell death is the stimulus attracting specialized phagocytes migrating into the developing visual system.…”

“…; Francisco‐Morcillo et al. ). During these phases, there has been observed occasional spatiotemporal coincidence of dying cells with macrophages and microglial precursors in the developing avian retina (Cuadros et al.…”

“…Phagocytosis has been considered to be the final stage of programmed cell death (PCD). PCD plays a crucial part during development of the vertebrate visual system (for a review, see Francisco-Morcillo et al 2014). However, PCD also occurs in this region of the central nervous system (CNS) under pathological and experimental conditions.…”