Evidence of a difference in photoreceptor cell loss in the peripheral versus posterior regions of the vitiligo (C57BL/6J-mivit/mivit) mouse retina

1995 ◽  
Vol 60 (3) ◽  
pp. 333-336 ◽  
Author(s):  
Sylvia B. Smith
Keyword(s):  
Photoreceptor Cell ◽  
Cell Loss ◽  
Mouse Retina

Long-term ERG analysis in the partially light-damaged mouse retina reveals regressive and compensatory changes

2006 ◽  
Vol 23 (1) ◽  
pp. 91-97 ◽  
Author(s):  
ADAM RICHARDS ◽  
ALFRED A. EMONDI ◽  
BAERBEL ROHRER
Keyword(s):  
Photoreceptor Cell ◽  
Light Exposure ◽  
Cell Loss ◽  
Oscillatory Potentials ◽  
Mouse Retina ◽  
Dependent Manner ◽  
Light Damage ◽  
Outer Retina ◽  
Inner Retina ◽  
Baseline Values

Most of the blinding retinopathies are due to progressive photoreceptor degeneration. Treatment paradigms that are currently being investigated include strategies to either halt or slow down photoreceptor cell loss, or to replace useful vision with retinal prosthesis. However, more information is required on the pathophysiological changes of the diseased retina, in particular the inner retina, that occur as a consequence of photoreceptor cell loss. Here we wished to use light damage as a stoppable insult to determine the structural and functional consequences on inner and outer retina, with the overall goal of determining whether survival of a functional inner retina is possible even if the outer retina is damaged. Mice were exposed to a 20-day light-damage period. Electroretinograms (ERG) and morphology were used to assess subsequent recovery. Outer retina was monitored analyzinga-waves, which represent photoreceptor cell responses, and histology. Integrity of the inner retina was monitored, analyzingb-waves and oscillatory potentials (OP1–OP4) and immunohistochemical markers for known proteins of the inner retina. All six ERG components were significantly suppressed with respect to amplitudes and kinetics, but stabilized in a wave-dependent manner within 40–70 days after the end of light exposure. As expected, damage of the outer retina was permanent. However, function of the inner retina was found to recover significantly. Whileb-wave amplitudes remained suppressed to 60% of their baseline values, OP amplitudes recovered completely, and implicit times of all components of the inner retina (b-wave and OP1–OP4) recovered to a level close to baseline values. Histological analyses confirmed the lack of permanent damage to the inner retina. In summary, these data suggests that the inner retina has the potential for significant recovery as well as plasticity if treatment is available to stop the deterioration of the outer retina.

scholarly journals A human model of Batten disease shows role of CLN3 in phagocytosis at the photoreceptor–RPE interface

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Cynthia Tang ◽  
Jimin Han ◽  
Sonal Dalvi ◽  
Kannan Manian ◽  
Lauren Winschel ◽  
...  
Keyword(s):  
Photoreceptor Cell ◽  
Vision Loss ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Cell Loss ◽  
Human Model ◽  
Lysosomal Storage ◽  
Rpe Cells ◽  
Cln3 Disease

AbstractMutations in CLN3 lead to photoreceptor cell loss in CLN3 disease, a lysosomal storage disorder characterized by childhood-onset vision loss, neurological impairment, and premature death. However, how CLN3 mutations cause photoreceptor cell death is not known. Here, we show that CLN3 is required for phagocytosis of photoreceptor outer segment (POS) by retinal pigment epithelium (RPE) cells, a cellular process essential for photoreceptor survival. Specifically, a proportion of CLN3 in human, mouse, and iPSC-RPE cells localized to RPE microvilli, the site of POS phagocytosis. Furthermore, patient-derived CLN3 disease iPSC-RPE cells showed decreased RPE microvilli density and reduced POS binding and ingestion. Notably, POS phagocytosis defect in CLN3 disease iPSC-RPE cells could be rescued by wild-type CLN3 gene supplementation. Altogether, these results illustrate a novel role of CLN3 in regulating POS phagocytosis and suggest a contribution of primary RPE dysfunction for photoreceptor cell loss in CLN3 disease that can be targeted by gene therapy.

scholarly journals Dysfunction of Heterotrimeric Kinesin-2 in Rod Photoreceptor Cells and the Role of Opsin Mislocalization in Rapid Cell Death

2010 ◽  
Vol 21 (23) ◽  
pp. 4076-4088 ◽  
Author(s):  
Vanda S. Lopes ◽  
David Jimeno ◽  
Kornnika Khanobdee ◽  
Xiaodan Song ◽  
Bryan Chen ◽  
...  
Keyword(s):  
Cell Death ◽  
Outer Segment ◽  
Photoreceptor Cell ◽  
Photoreceptor Cells ◽  
Cell Loss ◽  
Rod Photoreceptor ◽  
Retinal Degenerations ◽  
Cell Counts ◽  
And Function

Due to extensive elaboration of the photoreceptor cilium to form the outer segment, axonemal transport (IFT) in photoreceptors is extraordinarily busy, and retinal degeneration is a component of many ciliopathies. Functional loss of heterotrimeric kinesin-2, a major anterograde IFT motor, causes mislocalized opsin, followed by rapid cell death. Here, we have analyzed the nature of protein mislocalization and the requirements for the death of kinesin-2-mutant rod photoreceptors. Quantitative immuno EM showed that opsin accumulates initially within the inner segment, and then in the plasma membrane. The light-activated movement of arrestin to the outer segment is also impaired, but this defect likely results secondarily from binding to mislocalized opsin. Unlike some other retinal degenerations, neither opsin–arrestin complexes nor photoactivation were necessary for cell loss. In contrast, reduced rod opsin expression provided enhanced rod and cone photoreceptor survival and function, as measured by photoreceptor cell counts, apoptosis assays, and ERG analysis. The cell death incurred by loss of kinesin-2 function was almost completely negated by Rho−/−. Our results indicate that mislocalization of opsin is a major cause of photoreceptor cell death from kinesin-2 dysfunction and demonstrate the importance of accumulating mislocalized protein per se, rather than specific signaling properties of opsin, stemming from photoactivation or arrestin binding.

scholarly journals Mutations affecting development of the zebrafish retina

Development ◽  
1996 ◽  
Vol 123 (1) ◽  
pp. 263-273 ◽  
Author(s):  
J. Malicki ◽  
S.C. Neuhauss ◽  
A.F. Schier ◽  
L. Solnica-Krezel ◽  
D.L. Stemple ◽  
...  
Keyword(s):  
Retinal Degeneration ◽  
Large Scale ◽  
Photoreceptor Cell ◽  
Cell Loss ◽  
Retinal Neurons ◽  
Wild Type ◽  
Eye Growth ◽  
Layer 4 ◽  
Laminar Pattern ◽  
Zebrafish Embryogenesis

In a large scale screen for genetic defects in zebrafish embryogenesis we identified 49 mutations affecting development of the retina. Based on analysis of living embryos as well as histological sections, we grouped the isolated mutations into six phenotypic categories. (1) Mutations in three loci result in a loss of wild-type laminar pattern of the neural retina. (2) Defects in four loci lead to an abnormal specification of the eye anlagen. Only one eye frequently forms in this class of mutants. (3) Seven loci predominantly affect development of the outer retinal layers. Mutants in this category display cell loss mainly in the photoreceptor cell layer. (4) Nine mutations cause retardation of eye growth without any other obvious abnormalities in the retina. (5) A group of twelve mutations is characterized by nonspecific retinal degeneration. (6) Four mutations display retinal degeneration associated with a pigmentation defect. Finally, two mutations, one with absence of the ventral retina and one with an eye-specific pigmentation defect, are not classified in any of the above groups. The identified mutations affect numerous aspects of eye development, including: specification of the eye anlage, growth rate of the optic cup, establishment of retinal stratification, specification or differentiation of retinal neurons and formation of the dorsoventral axis in the developing eye.

Human ESC–derived retinal epithelial cell sheets potentiate rescue of photoreceptor cell loss in rats with retinal degeneration

2017 ◽  
Vol 9 (421) ◽  
pp. eaai7471 ◽  
Author(s):  
Karim Ben M’Barek ◽  
Walter Habeler ◽  
Alexandra Plancheron ◽  
Mohamed Jarraya ◽  
Florian Regent ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Retinal Degeneration ◽  
Photoreceptor Cell ◽  
Cell Loss ◽  
Cell Sheets

Compensatory synaptic growth in the rod terminals as a sequel to partial photoreceptor cell loss in the retina of chimaeric mice

Development ◽  
1992 ◽  
Vol 114 (3) ◽  
pp. 797-803
Author(s):  
S. Sanyal ◽  
R.K. Hawkins ◽  
H.G. Jansen ◽  
G.H. Zeilmaker
Keyword(s):  
Photoreceptor Cell ◽  
Three Dimensional ◽  
Photoreceptor Cells ◽  
Cell Loss ◽  
Afferent Input ◽  
Second Order ◽  
Visual Sensitivity ◽  
Synaptic Ribbons ◽  
Synaptic Growth ◽  
Initial Development

In the retina of chimaeric mice of rd and wild-type genotypic combination, selective loss of rd/rd photoreceptor cells, after initial development, leads to a mosaic retina with variable amounts of normal photoreceptor cells present over the retinal surface. In some of the rod terminals of these retinas the synaptic complexes with the second order retinal neurons are seen to contain multiple synaptic ribbons and an increased number of profiles of the postsynaptic elements. These changes are observed only in the rod terminals and not in the cone pedicles. Computer aided three-dimensional reconstruction of the altered synapses shows that these changes result from an increase in the number of synaptic sites, characterized by multiplication of the synaptic ribbons and enlargement of the second order neuronal processes. A quantitative analysis of such synapses, based on serial electron micrographs, shows that these are most frequently located in the retinal regions of the chimaeric individuals that have suffered maximum photoreceptor cell loss. Thus synaptic growth appears to take place as a reaction to the reduction of afferent input to the postsynaptic components. These findings demonstrate persistent synaptic plasticity in the rod terminals of mammalian retina during the maturational phase of late postnatal development. Compensatory synaptic growth in the rod terminals, as recorded here, can have important implications for the maintenance of visual sensitivity in the diseased or ageing retina.

scholarly journals Immunomodulation-accelerated neuronal regeneration following selective rod photoreceptor cell ablation in the zebrafish retina

2017 ◽  
Vol 114 (18) ◽  
pp. E3719-E3728 ◽  
Author(s):  
David T. White ◽  
Sumitra Sengupta ◽  
Meera T. Saxena ◽  
Qingguo Xu ◽  
Justin Hanes ◽  
...  
Keyword(s):  
Photoreceptor Cell ◽  
Immune Cell ◽  
Cell Loss ◽  
Innate Immune ◽  
Retinal Cell ◽  
Cell Regeneration ◽  
Rod Photoreceptor ◽  
Cell Replacement ◽  
Retinal Microglia ◽  
Rod Cell

Müller glia (MG) function as inducible retinal stem cells in zebrafish, completely repairing the eye after damage. The innate immune system has recently been shown to promote tissue regeneration in which classic wound-healing responses predominate. However, regulatory roles for leukocytes during cellular regeneration—i.e., selective cell-loss paradigms akin to degenerative disease—are less well defined. To investigate possible roles innate immune cells play during retinal cell regeneration, we used intravital microscopy to visualize neutrophil, macrophage, and retinal microglia responses to induced rod photoreceptor apoptosis. Neutrophils displayed no reactivity to rod cell loss. Peripheral macrophage cells responded to rod cell loss, as evidenced by morphological transitions and increased migration, but did not enter the retina. Retinal microglia displayed multiple hallmarks of immune cell activation: increased migration, translocation to the photoreceptor cell layer, proliferation, and phagocytosis of dying cells. To test function during rod cell regeneration, we coablated microglia and rod cells or applied immune suppression and quantified the kinetics of (i) rod cell clearance, (ii) MG/progenitor cell proliferation, and (iii) rod cell replacement. Coablation and immune suppressants applied before cell loss caused delays in MG/progenitor proliferation rates and slowed the rate of rod cell replacement. Conversely, immune suppressants applied after cell loss had been initiated led to accelerated photoreceptor regeneration kinetics, possibly by promoting rapid resolution of an acute immune response. Our findings suggest that microglia control MG responsiveness to photoreceptor loss and support the development of immune-targeted therapeutic strategies for reversing cell loss associated with degenerative retinal conditions.

scholarly journals Pigment Epithelium-Derived Factor (PEDF) Fragments Prevent Mouse Cone Photoreceptor Cell Loss Induced by Focal Phototoxicity In Vivo

2020 ◽  
Vol 21 (19) ◽  
pp. 7242
Author(s):  
Francisco J. Valiente-Soriano ◽  
Johnny Di Pierdomenico ◽  
Diego García-Ayuso ◽  
Arturo Ortín-Martínez ◽  
Juan A. Miralles de Imperial-Ollero ◽  
...  
Keyword(s):  
Photoreceptor Cell ◽  
Cell Damage ◽  
Pigment Epithelium ◽  
Cell Loss ◽  
Negative Control ◽  
Cone Photoreceptor ◽  
Peptide Fragments ◽  
Neurotrophic Activity ◽  
Pigment Epithelium Derived Factor

Here, we evaluated the effects of PEDF (pigment epithelium-derived factor) and PEDF peptides on cone-photoreceptor cell damage in a mouse model of focal LED-induced phototoxicity (LIP) in vivo. Swiss mice were dark-adapted overnight, anesthetized, and their left eyes were exposed to a blue LED placed over the cornea. Immediately after, intravitreal injection of PEDF, PEDF-peptide fragments 17-mer, 17-mer[H105A] or 17-mer[R99A] (all at 10 pmol) were administered into the left eye of each animal. BDNF (92 pmol) and bFGF (27 pmol) injections were positive controls, and vehicle negative control. After 7 days, LIP resulted in a consistent circular lesion located in the supratemporal quadrant and the number of S-cones were counted within an area centered on the lesion. Retinas treated with effectors had significantly greater S-cone numbers (PEDF (60%), 17-mer (56%), 17-mer [H105A] (57%), BDNF (64%) or bFGF (60%)) relative to their corresponding vehicle groups (≈42%). The 17-mer[R99A] with no PEDF receptor binding and no neurotrophic activity, PEDF combined with a molar excess of the PEDF receptor blocker P1 peptide, or with a PEDF-R enzymatic inhibitor had undetectable effects in S-cone survival. The findings demonstrated that the cone survival effects were mediated via interactions between the 17-mer region of the PEDF molecule and its PEDF-R receptor.

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