title: A role for the outer retina in development of the intrinsic pupillary light reflex in mice.
abstract: Mice do not require the brain in order to maintain constricted pupils. However, little is known about this intrinsic pupillary light reflex (iPLR) beyond a requirement for melanopsin in the iris and an intact retinal ciliary marginal zone (CMZ). Here, we study the mouse iPLR in vitro and examine a potential role for outer retina (rods and cones) in this response. In wild-type mice the iPLR was absent at postnatal day 17 (P17), developing progressively from P21-P49. However, the iPLR only achieved ∼ 30% of the wild-type constriction in adult mice with severe outer retinal degeneration (rd and rdcl). Paradoxically, the iPLR increased significantly in retinal degenerate mice >1.5 years of age. This was accompanied by an increase in baseline pupil tone in the dark to levels indistinguishable from those in adult wild types. This rejuvenated iPLR response was slowed by atropine application, suggesting the involvement of cholinergic neurotransmission. We could find no evidence of an increase in melanopsin expression by quantitative PCR in the iris and ciliary body of aged retinal degenerates and a detailed anatomical analysis revealed a significant decline in melanopsin-positive intrinsically photosensitive retinal ganglion cells (ipRGCs) in rdcl mice >1.5 years. Adult mice lacking rod function (Gnat1(-/-)) also had a weak iPLR, while mice lacking functional cones (Cpfl5) maintained a robust response. We also identify an important role for pigmentation in the development of the mouse iPLR, with only a weak and transient response present in albino animals. Our results show that the iPLR in mice develops unexpectedly late and are consistent with a role for rods and pigmentation in the development of this response in mice. The enhancement of the iPLR in aged degenerate mice was extremely surprising but may have relevance to behavioral observations in mice and patients with retinitis pigmentosa.
authors.affiliation: Department of Ocular Biology and Therapeutics, UCL-Institute of Ophthalmology, 11-43 Bath Street, London, UK. Electronic address: a.vugler@ucl.ac.uk.
authors.forename: A
authors.initials: A
authors.lastname: Vugler
authors.affiliation: Department of Ocular Biology and Therapeutics, UCL-Institute of Ophthalmology, 11-43 Bath Street, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Semo
authors.affiliation: Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, and Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Ortín-Martínez
authors.affiliation: Department of Ocular Biology and Therapeutics, UCL-Institute of Ophthalmology, 11-43 Bath Street, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Rojanasakul
authors.affiliation: Department of Ocular Biology and Therapeutics, UCL-Institute of Ophthalmology, 11-43 Bath Street, London, UK.
authors.forename: B
authors.initials: B
authors.lastname: Nommiste
authors.affiliation: Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, and Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain.
authors.forename: F J
authors.initials: FJ
authors.lastname: Valiente-Soriano
authors.affiliation: Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, and Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain.
authors.forename: D
authors.initials: D
authors.lastname: García-Ayuso
authors.affiliation: Department of Ocular Biology and Therapeutics, UCL-Institute of Ophthalmology, 11-43 Bath Street, London, UK.
authors.forename: P
authors.initials: P
authors.lastname: Coffey
authors.affiliation: Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, and Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Vidal-Sanz
authors.affiliation: Department of Ocular Biology and Therapeutics, UCL-Institute of Ophthalmology, 11-43 Bath Street, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Gias
mesh_terms: D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003623:Dark Adaptation; D055879:Gene Knock-In Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010775:Photic Stimulation; D012025:Reflex, Pupillary / Q000187:drug effects; D012160:Retina / Q000378:metabolism / Q000502:physiology*; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology; D017299:Rod Opsins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000099210:Melanopsin
chemical_list: D000109:Acetylcholine; D001285:Atropine; D018727:Muscarinic Antagonists; D017299:Rod Opsins; D000099210:Melanopsin
keywords: development; melanopsin; pigmentation; pupillary light reflex; rd mice; retinitis pigmentosa