A novel immunodeficient NOD.SCID-rd1 mouse model of retinitis pigmentosa to investigate potential therapeutics and pathogenesis of retinal degeneration

Retinitis pigmentosa (RP) is a common retinal degeneration disease caused by mutation in any gene of the photo transduction cascade and results in photoreceptor dystrophy. Over decades, several animal models have been used to address the need for the elucidation of effective therapeutics and factors...

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Main Authors: Alaknanda Mishra, Barun Das, Madhu Nath, Srikanth Iyer, Ashwani Kesarwani, Jashdeep Bhattacharjee, Shailendra Arindkar, Preeti Sahay, Kshama Jain, Parul Sahu, Prakriti Sinha, Thirumurthy Velpandian, Perumal Nagarajan, Pramod Upadhyay
Format: Article
Language:English
Published: The Company of Biologists 2017-04-01
Series:Biology Open
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Online Access:http://bio.biologists.org/content/6/4/449
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author Alaknanda Mishra
Barun Das
Madhu Nath
Srikanth Iyer
Ashwani Kesarwani
Jashdeep Bhattacharjee
Shailendra Arindkar
Preeti Sahay
Kshama Jain
Parul Sahu
Prakriti Sinha
Thirumurthy Velpandian
Perumal Nagarajan
Pramod Upadhyay
author_facet Alaknanda Mishra
Barun Das
Madhu Nath
Srikanth Iyer
Ashwani Kesarwani
Jashdeep Bhattacharjee
Shailendra Arindkar
Preeti Sahay
Kshama Jain
Parul Sahu
Prakriti Sinha
Thirumurthy Velpandian
Perumal Nagarajan
Pramod Upadhyay
author_sort Alaknanda Mishra
collection DOAJ
description Retinitis pigmentosa (RP) is a common retinal degeneration disease caused by mutation in any gene of the photo transduction cascade and results in photoreceptor dystrophy. Over decades, several animal models have been used to address the need for the elucidation of effective therapeutics and factors regulating retinal degeneration to prohibit or renew the damaged retina. However, controversies over the immune privilege of retina during cell transplantation and the role of immune modulation during RP still remain largely uninvestigated because of the lack of suitable animal models. Here, we have developed an immunocompromised mouse model, NOD.SCID-rd1, for retinitis pigmentosa (RP) by crossing CBA/J and NOD SCID mice and selecting homozygous double mutant animals for further breeding. Characterization of the newly developed RP model indicates a similar retinal degeneration pattern as CBA/J, with a decreased apoptosis rate and rhodopsin loss. It also exhibits loss of T cells, B cells and NK cells. The NOD.SCID-rd1 model is extremely useful for allogenic and xenogenic cell-based therapeutics, as indicated by the higher cell integration capacity post transplantation. We dissect the underlying role of the immune system in the progression of RP and the effect of immune deficiency on immune privilege of the eye using comparative qPCR studies of this model and the immune-competent RP model.
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spelling doaj.art-b6a901c473594178b46ea82b9446f0062022-12-21T19:48:17ZengThe Company of BiologistsBiology Open2046-63902017-04-016444946210.1242/bio.021618021618A novel immunodeficient NOD.SCID-rd1 mouse model of retinitis pigmentosa to investigate potential therapeutics and pathogenesis of retinal degenerationAlaknanda Mishra0Barun Das1Madhu Nath2Srikanth Iyer3Ashwani Kesarwani4Jashdeep Bhattacharjee5Shailendra Arindkar6Preeti Sahay7Kshama Jain8Parul Sahu9Prakriti Sinha10Thirumurthy Velpandian11Perumal Nagarajan12Pramod Upadhyay13 Product Development Cell-1, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India Product Development Cell-1, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India Department of Ocular Pharmacology, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi 110029, India Product Development Cell-1, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India Product Development Cell-1, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India Product Development Cell-1, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India Product Development Cell-1, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India Product Development Cell-1, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India Product Development Cell-1, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India Product Development Cell-1, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India Product Development Cell-1, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India Department of Ocular Pharmacology, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi 110029, India Product Development Cell-1, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India Product Development Cell-1, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India Retinitis pigmentosa (RP) is a common retinal degeneration disease caused by mutation in any gene of the photo transduction cascade and results in photoreceptor dystrophy. Over decades, several animal models have been used to address the need for the elucidation of effective therapeutics and factors regulating retinal degeneration to prohibit or renew the damaged retina. However, controversies over the immune privilege of retina during cell transplantation and the role of immune modulation during RP still remain largely uninvestigated because of the lack of suitable animal models. Here, we have developed an immunocompromised mouse model, NOD.SCID-rd1, for retinitis pigmentosa (RP) by crossing CBA/J and NOD SCID mice and selecting homozygous double mutant animals for further breeding. Characterization of the newly developed RP model indicates a similar retinal degeneration pattern as CBA/J, with a decreased apoptosis rate and rhodopsin loss. It also exhibits loss of T cells, B cells and NK cells. The NOD.SCID-rd1 model is extremely useful for allogenic and xenogenic cell-based therapeutics, as indicated by the higher cell integration capacity post transplantation. We dissect the underlying role of the immune system in the progression of RP and the effect of immune deficiency on immune privilege of the eye using comparative qPCR studies of this model and the immune-competent RP model.http://bio.biologists.org/content/6/4/449Retinitis pigmentosaNOD.SCID-rd1 mouse modelImmunocompromised mouseCell based therapeutics
spellingShingle Alaknanda Mishra
Barun Das
Madhu Nath
Srikanth Iyer
Ashwani Kesarwani
Jashdeep Bhattacharjee
Shailendra Arindkar
Preeti Sahay
Kshama Jain
Parul Sahu
Prakriti Sinha
Thirumurthy Velpandian
Perumal Nagarajan
Pramod Upadhyay
A novel immunodeficient NOD.SCID-rd1 mouse model of retinitis pigmentosa to investigate potential therapeutics and pathogenesis of retinal degeneration
Biology Open
Retinitis pigmentosa
NOD.SCID-rd1 mouse model
Immunocompromised mouse
Cell based therapeutics
title A novel immunodeficient NOD.SCID-rd1 mouse model of retinitis pigmentosa to investigate potential therapeutics and pathogenesis of retinal degeneration
title_full A novel immunodeficient NOD.SCID-rd1 mouse model of retinitis pigmentosa to investigate potential therapeutics and pathogenesis of retinal degeneration
title_fullStr A novel immunodeficient NOD.SCID-rd1 mouse model of retinitis pigmentosa to investigate potential therapeutics and pathogenesis of retinal degeneration
title_full_unstemmed A novel immunodeficient NOD.SCID-rd1 mouse model of retinitis pigmentosa to investigate potential therapeutics and pathogenesis of retinal degeneration
title_short A novel immunodeficient NOD.SCID-rd1 mouse model of retinitis pigmentosa to investigate potential therapeutics and pathogenesis of retinal degeneration
title_sort novel immunodeficient nod scid rd1 mouse model of retinitis pigmentosa to investigate potential therapeutics and pathogenesis of retinal degeneration
topic Retinitis pigmentosa
NOD.SCID-rd1 mouse model
Immunocompromised mouse
Cell based therapeutics
url http://bio.biologists.org/content/6/4/449
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