June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Role of nitric oxide and glutamate in retinitis pigmentosa: administration of nitric oxide synthase inhibitors
Author Affiliations & Notes
  • Maria Miranda
    Ciencias Biomédicas, Universidad CEU Cardenal Herrera Facultad de Ciencias de la Salud, Moncada, Valenciana, Spain
  • Antolin Cantó
    Ciencias Biomédicas, Universidad CEU Cardenal Herrera Facultad de Ciencias de la Salud, Moncada, Valenciana, Spain
  • Javier Martínez
    Ciencias Biomédicas, Universidad CEU Cardenal Herrera Facultad de Ciencias de la Salud, Moncada, Valenciana, Spain
  • Vicente Hernández-Rabaza
    Ciencias Biomédicas, Universidad CEU Cardenal Herrera Facultad de Ciencias de la Salud, Moncada, Valenciana, Spain
  • Rosa López-Pedrajas
    Ciencias Biomédicas, Universidad CEU Cardenal Herrera Facultad de Ciencias de la Salud, Moncada, Valenciana, Spain
  • Teresa Olivar
    Ciencias Biomédicas, Universidad CEU Cardenal Herrera Facultad de Ciencias de la Salud, Moncada, Valenciana, Spain
  • Inmaculada Almansa
    Ciencias Biomédicas, Universidad CEU Cardenal Herrera Facultad de Ciencias de la Salud, Moncada, Valenciana, Spain
  • Footnotes
    Commercial Relationships   Maria Miranda None; Antolin Cantó None; Javier Martínez None; Vicente Hernández-Rabaza None; Rosa López-Pedrajas None; Teresa Olivar None; Inmaculada Almansa None
  • Footnotes
    Support  ACIF 199/2019, FPU20/06277, INDI21/39
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 5067. doi:
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      Maria Miranda, Antolin Cantó, Javier Martínez, Vicente Hernández-Rabaza, Rosa López-Pedrajas, Teresa Olivar, Inmaculada Almansa; Role of nitric oxide and glutamate in retinitis pigmentosa: administration of nitric oxide synthase inhibitors. Invest. Ophthalmol. Vis. Sci. 2023;64(8):5067.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Nitric oxide (NO) is a gas and signaling molecule with important functions in the visual system. It modulates visual transduction and stimulates guanylate cyclase and cyclic guanosine monophosphate (cGMP) production. cGMP is a critical molecule in the phototransduction cascade in the retina of vertebrates. NO is also a vascular endothelial relaxant and is regulates ocular blood flow.
NO underproduction has been related with glaucoma and a NO excess may be imvolved in other retinal pathologies such as retinitis pigmentosa (RP). RP is a retinal hereditary disease characterized by rod degeneration followed by cone degeneration. RP has been related with accumulation in cGMP, glutamate and calcium. The purpose of this study was, therefore, to study NO metabolism and the NO-cGMP axis in the retina of different RP animal models and to demonstrate possible alterations that may contribute to photoreceptor death.

Methods : Animals were treated in accordance with the ARVO statement for the use of animals in ophthalmic and vision research. Rd1, rd10 and rds mice were used in this study. Mice were sacrificed at different postnatal days (11, 17, 21, and 28). Retinal glutamate concentrations were determined by high pressure liquid chromatography (HPLC). The expression of different enzymes responsible for NO production (neuronal or inducible nitric oxide synthases (nNOS or iNOS)) was determined by histochemistry or by western blot. Finally, a NOS inhibitor (such as dutasteride) was administered intraperitoneally to rds mice on postnatal days 11, 13, 15, 17 and 19 and euthanized on day 21. TUNEL, was performed to determine if DUT was able to delay photoreceptor death. Immunohistochemical and HPLC techniques were used to study if dutasteride was also able to reverse possible alterations in NO metabolism.

Results : Glutamate, the major excitatory neurotransmitter in central nervous system, as well as nNOS was observed to be increased in the retina of three different RP animal models at different time points, mainly between the peak of rods and cones death. Administration of a NOS inhibitor to rds mice was able to restore the observed alterations in NO metabolism and to increase photoreceptor survival.

Conclusions : There are alterations in the expression of nNOS and glutamate in three different animal models of RP. The use of NOS inhibitors may be useful as a treatment in RP.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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