Long-Term In Vivo Imaging and Measurement of Dendritic Shrinkage of Retinal Ganglion Cells

Leung, Christopher Kai-Shun; Weinreb, Robert N.; Li, Zhi Wei; Liu, Shu; Lindsey, James D.; Choi, Nathan; Liu, Lan; Cheung, Carol Y.; Ye, Cong; Qiu, Kunliang; Chen, Li Jia; Yung, Wing‐Ho; Crowston, Jonathan G; Pu, Mingliang; So, Kwok-Fai; Pang, Chi Pui; Lam, Dennis Shun Chiu

doi:10.1167/iovs.10-6012

Cited by 105 publications

(113 citation statements)

References 24 publications

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“…To investigate the dynamics such as disease progression and the short-term dynamics such as cell-cell interaction to be monitored and quantified in individual animals. [19][20][21][22][23] Because an SLO relies on the mouse eye as the objective lens, the image quality depends heavily on the mouse eye optical parameters. The numerical aperture of the mouse eye has been reported to be as high as 0.5, approximately 2.5 times as large as that of the fully dilated human eye.…”

Section: Discussionmentioning

confidence: 99%

In vivo tracking of hematopoietic cells in the retina of chimeric mice with a scanning laser ophthalmoscope

et al. 2012

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Section: Discussionmentioning

confidence: 99%

In vivo tracking of hematopoietic cells in the retina of chimeric mice with a scanning laser ophthalmoscope

et al. 2012

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“…With this strain characterization of at least six different RGC types has been accomplished ex vivo 51 and in vivo. 52 The ability to monitor live cells and measure parameters such as soma size, dendritic length, dendritic arbor and dendritic complexity can provide detailed information on how RGCs respond to different types of injury. 52,53 The Thy1-YFP transgenic mouse has provided evidence that dendritic changes can be an early indicator of RGC damage and these structural changes are detectable with in vivo imaging (Figure 4).…”

Section: Transgenic Animalsmentioning

confidence: 99%

“…52 The ability to monitor live cells and measure parameters such as soma size, dendritic length, dendritic arbor and dendritic complexity can provide detailed information on how RGCs respond to different types of injury. 52,53 The Thy1-YFP transgenic mouse has provided evidence that dendritic changes can be an early indicator of RGC damage and these structural changes are detectable with in vivo imaging (Figure 4). Visualizing and measuring dendritic atrophy of RGCs can be useful for studying the effects of neuroprotective interventions in the early stages of damage.…”

Section: Transgenic Animalsmentioning

confidence: 99%

Assessing retinal ganglion cell damage

Smith

Vianna

Chauhan

2017

Eye

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Retinal ganglion cell (RGC) loss is the hallmark of optic neuropathies, including glaucoma, where damage to RGC axons occurs at the level of the optic nerve head. In experimental glaucoma, damage is assessed at the axon level (in the retinal nerve fibre layer and optic nerve head) or at the soma level (in the retina). In clinical glaucoma where measurements are generally limited to non-invasive techniques, structural measurements of the retinal nerve fibre layer and optic nerve head, or functional measurements with perimetry provide surrogate estimates of RGC integrity. These surrogate measurements, while clinically useful, are several levels removed from estimating actual RGC loss. Advances in imaging, labelling techniques, and transgenic medicine are making enormous strides in experimental glaucoma, providing knowledge on the pathophysiology of glaucoma, its progression and testing new therapeutic avenues. Advances are also being made in functional imaging of RGCs. Future efforts will now be directed towards translating these advances to clinical care.

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“…Type specifi c degeneration has been noted in the primate (Weber et al, 1998 ), cat (Shou et al, 2003 ), mouse (Leung et al, 2011 ;Feng et al, 2013 ), and rat (Thanos, 1988 ) but not in DBA/2J (Jakobs et al, 2005 ) or thy1-YFP-H transgenic mice with experimental glaucoma (Kalesnykas et al, 2012 ). The Sholl plots in Fig.…”

Section: Discussionmentioning

confidence: 91%

A novel system for the classification of diseased retinal ganglion cells

et al. 2014

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Retinal ganglion cell (RGC) dendritic atrophy is an early feature of many forms of retinal degeneration, providing a challenge to RGC classifi cation. The characterization of these changes is complicated by the possibility that selective labeling of any particular class can confound the estimation of dendritic remodeling. To address this issue we have developed a novel, robust, and quantitative RGC classifi cation based on proximal dendritic features which are resistant to early degeneration. RGCs were labeled through the ballistic delivery of DiO and DiI coated tungsten particles to whole retinal explants of 20 adult Brown Norway rats. RGCs were grouped according to the Sun classifi cation system. A comprehensive set of primary and secondary dendrite features were quantifi ed and a new classifi cation model derived using principal component (PCA) and discriminant analyses, to estimate the likelihood that a cell belonged to any given class. One-hundred and thirty one imaged RGCs were analyzed; according to the Sun classifi cation, 24% ( n = 31) were RGC A , 29% ( n = 38) RGC B , 32% ( n = 42) RGC C , and 15% ( n = 20) RGC D . PCA gave a 3 component solution, separating RGCs based on descriptors of soma size and primary dendrite thickness, proximal dendritic fi eld size and dendritic tree asymmetry. The new variables correctly classifi ed 73.3% ( n = 74) of RGCs from a training sample and 63.3% ( n = 19) from a hold out sample indicating an effective model. Soma and proximal dendritic tree morphological features provide a useful surrogate measurement for the classifi cation of RGCs in disease. While a defi nitive classifi cation is not possible in every case, the technique provides a useful safeguard against sample bias where the normal criteria for cell classifi cation may not be reliable.

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Long-Term In Vivo Imaging and Measurement of Dendritic Shrinkage of Retinal Ganglion Cells

Abstract: Estimating the probability of RGC survival and measuring the rate of dendritic shrinkage could become a new paradigm for investigating neuronal degeneration and evaluating the response of neuroprotective treatment.

Cited by 105 publications

References 24 publications

In vivo tracking of hematopoietic cells in the retina of chimeric mice with a scanning laser ophthalmoscope

In vivo tracking of hematopoietic cells in the retina of chimeric mice with a scanning laser ophthalmoscope

Assessing retinal ganglion cell damage

A novel system for the classification of diseased retinal ganglion cells

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