The Rd8 mutation of the Crb1 gene is present in vendor lines of C57BL/6N mice and embryonic stem cells

This is an important issue for anyone involved in using murine models of retinal degeneration.  It turns out that contamination of Rd8 mutation in the B6 mice is more wide spread than the C57BL/6N mice.  Labs worldwide are going to have to reassess their data due to this mutation and all reviewers will ask about this in the immediate future.  The genotyping analysis of a variety of vendor lines is described in this paper by Mary J. Mattapallil, Eric F. Wawrousek, Chi-Chao Chan, Hui Zhao, Jayeeta Roychoudhury, Thomas A. Ferguson, and Rachel R. Caspi.  The take home message is that the rd8 mutation is in the C57BL/6N strain which is used worldwide to produce transgenic and knockout models.  The implications for non-vision labs are not as clear, but for vision labs, substantial disease can be present unrelated to another specific disease gene and will need to be accounted for.

Undersized Dendritic Arborizations in Retinal Ganglion Cells of the rd1 Mutant Mouse: A Paradigm of Early Onset Photoreceptor Degeneration

This paper by Devid Damiani, Elena Novelli, Francesca Mazzoni and Enrica Strettoi documents continued negative plasticity in retina by examining ganglion cells in the rd1 mouse.  The rd1 mouse is one of many models of retinal degenerative disease, in this case as an autosomal recessive retinal degenerative disease.  This work gets at the remodeling issue in retinal degenerative diseaseby examining the last cells in the chain of retinal cells that process information before sending it out to the brain and other CNS centers for further processing.   Continue reading “Undersized Dendritic Arborizations in Retinal Ganglion Cells of the rd1 Mutant Mouse: A Paradigm of Early Onset Photoreceptor Degeneration”

Long-Term Characterization of Retinal Degeneration in rd1 and rd10 Mice Using Spectral Domain Optical Coherence Tomography

This study by Mark E. Pennesi, Keith V. Michaels, Sienna S. Magee, Anastasiya Maricle, Sean P. Davin, Anupam K. Garg, Michael J. Gale, Daniel C. Tu, Yuquan Wen, Laura R. Erker, and Peter J. Francis documents the use of SD-OCT as a robust, non-invasive method for monitoring retinal changes in vivo in rodent models of retinal degeneration.  The approach is so good that it can discriminate retinal detachment differences in different models of retinal degeneration (rd1 and rd10) that share defects on the same gene.

While histology is still the gold standard, this paper documents the further push of new technologies into in vivo approaches of monitoring.  Perhaps we’ll get another boost with 2-photon/OCT approaches coming onto the scene…

Metabolic Differentiation In The Embryonic Retina

Michalis Agathocleous, Nicola K. Love, Owen Randlett, Julia J. Harris, Jinyue Liu, Andrew J. Murray and William A. Harris have published a very interesting story on proliferating cells of the Xenopus laevis retina that documents aerobic glycolysis rather than oxidative phosphorylation.  Historically, this shift in metabolism was termed the Warburg effect where it was originally described in tumorigenesis.  Could it be that this shift in metabolism is more widely used than previously anticipated?  Certainly in the proliferating developing Xenopus laevis retina, it appears so, even in the presence of oxygen.  The only other instance of aerobic glycolosis I am aware of is in T-cells, but that too is associated with oncogenicity.

This really opens up possibilities for metabolic control of a variety of processes in not only development, but also pathology with respect to alternative methods for defining metabolic states and deriving energy.

Full-Length Axon Regeneration In The Adult Mouse Optic Nerve and Partial Recovery of Simple Visual Behaviors

Friend of Webvision Yves Sauvé sent in this paper by Silmara de Lima, Yoshiki Koriyama, Takuji Kurimoto, Julia Teixeira Oliveira, Yuqin Yin, Yiqing Li, Hui-Ya Gilbert, Michela Fagiolini, Ana Maria Blanco Martinez, and Larry Benowitz that documents regeneration of the optic nerve in the adult mouse, a potentially substantial breakthrough in therapeutic recovery of vision lost through disease or trauma.

Continue reading “Full-Length Axon Regeneration In The Adult Mouse Optic Nerve and Partial Recovery of Simple Visual Behaviors”

Functional and Anatomical Remodeling in Human Retinal Detachment

This manuscript by Clairton F de Souza, Michael Kalloniatis, Philip J Polkinghorne, Charles N J McGhee and Monica L Acosta examined retinal remodeling in response to a form of retinal detachment.  Rhegmatogenous retinal detachment.  The authors describe the changes observed and note that retinal plasticity is acute and likely occurs quickly enough that it may explain persistent vision loss post-reattachment.  They also later conclude that retinal detachment, particularly with macular involvement is an emergent condition which is a fundamentally important conclusion.

Continue reading “Functional and Anatomical Remodeling in Human Retinal Detachment”

Microglia Sculpt Postnatal Neural Circuits In An Activity And Complement-Dependent Manner

This very cool study by Dorothy P. Schafer, Emily K. Lehrman, Amanda G. Kautzman, Ryuta Koyama, Alan R. Mardinly, Ryo Yamasaki, Richard M. Ransohoff, Michael E. Greenberg, Ben A. Barres and Beth Stevens demonstrates how the immune system can participate in the circuitry of the developing mouse lateral genicular nucleus (LGN).

Continue reading “Microglia Sculpt Postnatal Neural Circuits In An Activity And Complement-Dependent Manner”

Notable Paper: Network Deficiency Exacerbates Impairment in a Mouse Model of Retinal Degeneration

This paper by Christopher W. Yee, Abduqodir H. Toychiev and Botir T. Sagdullaev examines the role that neural oscillations play in normal and pathological states.  In a neurodegenerative model of retinitis pigmentosa, the authors examined the activity of neural networks in the rd1 mouse model and compared that activity to the wild type.   Continue reading “Notable Paper: Network Deficiency Exacerbates Impairment in a Mouse Model of Retinal Degeneration”

Dysmorphic Photoreceptors in a P23H Mutant Rhodopsin Model of Retinitis Pigmentosa Are Metabolically Active and Capable of Regenerating to Reverse Retinal Degeneration

This paper (and the cover article) is the result of a collaborative effort between Damian C. Lee, Felix R. Vazquez-Chona, W. Drew Ferrell, Beatrice M. Tam, Bryan W. JonesRobert E. Marc, and Orson L. Moritz.

Continue reading “Dysmorphic Photoreceptors in a P23H Mutant Rhodopsin Model of Retinitis Pigmentosa Are Metabolically Active and Capable of Regenerating to Reverse Retinal Degeneration”

Notable Paper: Gene Therapy Rescues Photoreceptor Blindness in Dogs and Paves The Way for Treating Human X-linked Retinitis Pigmentosa

This paper in PNAS by William A. Beltran, Artur V. Cideciyan, Alfred S. Lewin, Simone Iwabe, Hemant Khanna, Alexander Sumaroka, Vince A. Chiodo, Diego S. Fajardo, Alejandro J. Román, Wen-Tao Deng, Malgorzata Swider, Tomas S. Alemán, Sanford L. Boye, Sem Genini, Anand Swaroop, William W. Hauswirth, Samuel G. Jacobson and Gustavo D. Aguirre is a continuation of their work in retinal degeneration, this form of retinal degeneration, X-linked retinitis pigmentosa (RP).

Continue reading “Notable Paper: Gene Therapy Rescues Photoreceptor Blindness in Dogs and Paves The Way for Treating Human X-linked Retinitis Pigmentosa”

Generation of An Inbred Miniature Pig Model of Retinitis Pigmentosa

A recent paper by Jason W. Ross, Juan P. Fernandez de Castro, Jianguo Zhao, Melissa Samuel, Eric Walters, Cecilia Rios, Patricia Bray-Ward, Bryan W. JonesRobert E. MarcWei Wang, Liang Zhou, Jennifer M. Noel, Maureen A. McCallPaul J. DeMarcoRandall S. Prather and Henry J. Kaplan describes the creation of a new model of retinal degenerative disease, specifically autosomal dominant retinitis pigmentosa in a miniature pig model, serving as an additional tool to study these diseases and therapeutic interventions.

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Jumping Spiders Use Image Defocusing For Depth Perception

A study out in today’s Science Magazine by Takashi Nagata, Mitsumasa Koyanagi, Hisao Tsukamoto, Shinjiro Saeki, Kunio Isono, Yoshinori Shichida, Fumio Tokunaga, Michiyo Kinoshita, Kentaro Arikawa and Akihisa Terakita proposes that jumping spiders at least, use image defocusing to provide depth perception.  Jumping spiders (Salticidae) are the largest family of spiders and have perhaps the best visual acuity of the invertebrates.

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Astrocyte pVHL and HIF-α Isoforms Are Required for Embryonic-To-Adult Vascular Transition In The Eye

This paper from Toshihide Kurihara, Peter Westenskow, Tim Krohne, Edith Aguilar, Randy A. Johnson, and Marty Friedlander propose a model for the transition from embryonic to adult circulation in the eye  using a combinatorial gene deletion approach with over expression assays, examining astrocyte-targeted deletion of von Hippel-Lindau tumor suppressor (Vhl), hypoxia-inducible factor-αs (Hif-αs), and VEGF on normal regression of hyaloid vessels which are transient fetal vessels in the eye that can be seen in the second and early third trimester of human pregnancy.  Continue reading “Astrocyte pVHL and HIF-α Isoforms Are Required for Embryonic-To-Adult Vascular Transition In The Eye”