title: A novel immunodeficient NOD.SCID-rd1mouse model of retinitis pigmentosa to investigate potential therapeutics and pathogenesis of retinal degeneration.
abstract: 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-rd1model 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.
authors.affiliation: Product Development Cell-1, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Alaknanda
authors.initials: A
authors.lastname: Mishra
authors.affiliation: Product Development Cell-1, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Barun
authors.initials: B
authors.lastname: Das
authors.affiliation: Department of Ocular Pharmacology, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi 110029, India.
authors.forename: Madhu
authors.initials: M
authors.lastname: Nath
authors.affiliation: Product Development Cell-1, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Srikanth
authors.initials: S
authors.lastname: Iyer
authors.affiliation: Product Development Cell-1, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Ashwani
authors.initials: A
authors.lastname: Kesarwani
authors.affiliation: Product Development Cell-1, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Jashdeep
authors.initials: J
authors.lastname: Bhattacharjee
authors.affiliation: Product Development Cell-1, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Shailendra
authors.initials: S
authors.lastname: Arindkar
authors.affiliation: Product Development Cell-1, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Preeti
authors.initials: P
authors.lastname: Sahay
authors.affiliation: Product Development Cell-1, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Kshama
authors.initials: K
authors.lastname: Jain
authors.affiliation: Product Development Cell-1, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Parul
authors.initials: P
authors.lastname: Sahu
authors.affiliation: Product Development Cell-1, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Prakriti
authors.initials: P
authors.lastname: Sinha
authors.affiliation: Department of Ocular Pharmacology, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi 110029, India.
authors.forename: Thirumurthy
authors.initials: T
authors.lastname: Velpandian
authors.affiliation: Product Development Cell-1, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Perumal
authors.initials: P
authors.lastname: Nagarajan
authors.affiliation: Product Development Cell-1, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India pkumar@nii.ac.in.
authors.forename: Pramod
authors.identifier: http://orcid.org/0000-0002-5560-822X
authors.initials: P
authors.lastname: Upadhyay
keywords: Cell based therapeutics; Immunocompromised mouse; NOD.SCID-rd1 mouse model; Retinitis pigmentosa