Undersized dendritic arborizations in retinal ganglion cells of the rd1 mutant mouse: A paradigm of early onset photoreceptor degeneration

Damiani, Devid; Novelli, Elena; Mazzoni, Francesca; Strettoi, Enrica

doi:10.1002/cne.22802

Cited by 46 publications

(57 citation statements)

References 69 publications

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“…Therefore, optogenetic treatment that targets bipolar cells or photoreceptors (the latter even more so) may be questionable in patients with advanced stages of retinal degeneration. In contrast, retinal ganglion cells were reported to be the most resistant to remodeling (Damiani et al 2012, Mazzoni et al 2008). In the case of advanced severe retinal degenerations, retinal ganglion cells could be the only plausible target for optogenetic therapies.…”

Section: Developing Multiple Targeted Approachesmentioning

confidence: 88%

Optogenetic Approaches to Restoring Vision

Pan

2015

Annu. Rev. Vis. Sci.

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Severe loss of photoreceptor cells in inherited or acquired retinal degenerative diseases can result in partial loss of sight or complete blindness. The optogenetic strategy for restoration of vision utilizes optogenetic tools to convert surviving inner retinal neurons into photosensitive cells; thus, light sensitivity is imparted to the retina after the death of photoreceptor cells. Proof-of-concept studies, especially those using microbial rhodopsins, have demonstrated restoration of light responses in surviving retinal neurons and visually guided behaviors in animal models. Significant progress has also been made in improving microbial rhodopsin-based optogenetic tools, developing virus-mediated gene delivery, and targeting specific retinal neurons and subcellular compartments of retinal ganglion cells. In this article, we review the current status of the field and outline further directions and challenges to the advancement of this strategy toward clinical application and improvement in the outcomes of restored vision.

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Section: Developing Multiple Targeted Approachesmentioning

confidence: 88%

Optogenetic Approaches to Restoring Vision

Pan

2015

Annu. Rev. Vis. Sci.

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“…However, it should be emphasized that even diseases in which the same cell type degenerates may not share a common outcome, as in some models cell death occurs during development while in others the cell loss can be after maturity. For example, in the rd1 RP model, about half the retinal ganglion cell population develops smaller arbors (Damiani et al, 2012). But, in the rd10 mouse model for RP, retinal ganglion cell dendritic arbors appear normal (Mazzoni et al, 2008).…”

Section: Disease: Alterations To Structure and Functionmentioning

confidence: 99%

Functional architecture of the retina: Development and disease

Hoon

Okawa

Santina

et al. 2014

Progress in Retinal and Eye Research

467

385

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Structure and function are highly correlated in the vertebrate retina, a sensory tissue that is organized into cell layers with microcircuits working in parallel and together to encode visual information. All vertebrate retinas share a fundamental plan, comprising five major neuronal cell classes with cell body distributions and connectivity arranged in stereotypic patterns. Conserved features in retinal design have enabled detailed analysis and comparisons of structure, connectivity and function across species. Each species, however, can adopt structural and/or functional retinal specializations, implementing variations to the basic design in order to satisfy unique requirements in visual function. Recent advances in molecular tools, imaging and electrophysiological approaches have greatly facilitated identification of the cellular and molecular mechanisms that establish the fundamental organization of the retina and the specializations of its microcircuits during development. Here, we review advances in our understanding of how these mechanisms act to shape structure and function at the single cell level, to coordinate the assembly of cell populations, and to define their specific circuitry. We also highlight how structure is rearranged and function is disrupted in disease, and discuss current approaches to re-establish the intricate functional architecture of the retina.

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“…Additional Foxg1 +/+ and Foxg1 +/Cre mice were used for counting cells in the ganglion cell layer (GCL) following published protocols (Damiani et al, 2012, Rodriguez et al, 2014. Briefly, paraformaldheyde fixed retinas (n=3 per strain, each from a different animal) were isolated from eye cups, the vitreous removed and 4 partial cuts made to delimitate the dorsal, nasal, ventral and temporal quadrants.…”

Section: Counts Of Cells In the Ganglion Cell Layer (Gcl)mentioning

confidence: 99%

Visual impairment in FOXG1-mutated individuals and mice

et al. 2016

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The Forkead Box G1 (FOXG1) gene encodes for a DNA−binding transcription factor, essential for the development of the telencephalon in mammalian forebrain. Mutations in FOXG1 have been reported to be involved in the onset of Rett Syndrome, for which sequence alterations of MECP2 and CDKL5 are known. While visual alterations are not classical hallmarks of Rett syndrome, an increasing body of evidence shows visual impairment in patients and in MeCP2 and CDKL5 animal models. Herein we focused on the functional role of FOXG1 in the visual system of animal models (Foxg1+/Cre mice) and of a cohort of patients carrying FOXG1 mutations or deletions. Visual physiology of Foxg1+/Cre mice was assessed by visually evoked potentials, which revealed a significant reduction in response amplitude and visual acuity with respect to wild-type littermates. Morphological investigation showed abnormalities in the organization of excitatory/inhibitory circuits in the visual cortex. No alterations were observed in retinal structure. By examining a cohort of FOXG1-mutated patients by means of a panel of neuro-ophthalmological evaluations, we found that all of them exhibited visual alterations compatible with high level visual dysfunctions. In conclusion our data show that Foxg1 haploinsufficiency results in an impairment of mouse and patient visual function. Response to Reviewers: Pisa February 27th 2016Dear Editor, We would like to thank the referees for the thoughtful critiques on our manuscript and for the opportunity to revise our work. Please find enclosed a revised version of our manuscript (NSC-15-1232) entitled "Visual impairment in FOXG1-mutated patients and mice" by Boggio et al. As requested, we performed additional experiments on retina and visual cortex in order to more quantitavely prove the structure specific alterations and strengthen our conclusions. We included below a detailed response to the reviewer comments (in italics). References have been updated and added as suggested by referees. Sincerely, Tommaso PizzorussoReviewer #1:Major concerns 1.The description of the morphology of the five classes of retinal neurons would benefit from a quantitative approach amenable to statistical comparisons, similar to that performed for cortical GABAergic neurons in Fig. 4.We performed the requested quantitative analysis that is now shown in fig. 4. The analysis was focussed on cells in the ganglion cell layer because this layer is known to be affected in Foxg1 null mice. No significant change in the overall number of cells, and in ganglion cells identified using the RBPMS cell type-specific antibody, was present in Foxg1 heterozygous mice 2.There are no explicit statements regarding blinding of investigators to mouse genotypes during data acquisition and analyses, the use of Power Analysis to determine sample sizes, and predetermined criteria to exclude data sets. These are all critical issues that need to be performed and explicitly reported as recommended (Landis et al. Nature 2012).We included in the methods the fol...

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Undersized dendritic arborizations in retinal ganglion cells of the rd1 mutant mouse: A paradigm of early onset photoreceptor degeneration

Cited by 46 publications

References 69 publications

Optogenetic Approaches to Restoring Vision

Optogenetic Approaches to Restoring Vision

Functional architecture of the retina: Development and disease

Visual impairment in FOXG1-mutated individuals and mice

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