June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Dutasteride: possible new treatment in retinal degenerations
Author Affiliations & Notes
  • Maria Miranda
    Ciencias Biomédicas, Universidad CEU Cardenal Herrera Facultad de Ciencias de la Salud, Alfara, Valenciana, Spain
  • Antolin Cantó
    Ciencias Biomédicas, Universidad CEU Cardenal Herrera Facultad de Ciencias de la Salud, Alfara, Valenciana, Spain
  • Javier Martínez
    Ciencias Biomédicas, Universidad CEU Cardenal Herrera Facultad de Ciencias de la Salud, Alfara, Valenciana, Spain
  • Vicente Hernández-Rabaza
    Ciencias Biomédicas, Universidad CEU Cardenal Herrera Facultad de Ciencias de la Salud, Alfara, Valenciana, Spain
  • Teresa Olivar
    Ciencias Biomédicas, Universidad CEU Cardenal Herrera Facultad de Ciencias de la Salud, Alfara, Valenciana, Spain
  • Inmaculada Almansa
    Ciencias Biomédicas, Universidad CEU Cardenal Herrera Facultad de Ciencias de la Salud, Alfara, Valenciana, Spain
  • Footnotes
    Commercial Relationships   Maria Miranda None; Antolin Cantó None; Javier Martínez None; Vicente Hernández-Rabaza None; Teresa Olivar None; Inmaculada Almansa None
  • Footnotes
    Support  ACIF 199/2019, FPU20/06277, INDI21/39
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 3164 – F0438. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Maria Miranda, Antolin Cantó, Javier Martínez, Vicente Hernández-Rabaza, Teresa Olivar, Inmaculada Almansa; Dutasteride: possible new treatment in retinal degenerations. Invest. Ophthalmol. Vis. Sci. 2022;63(7):3164 – F0438.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : The interactions between gonadal steroid hormones and the retina have received limited attention, though it has been suggested that they may play a protective role in retinal diseases. The purpose of this work was to study the repurposing of one drug (dutasteride) for retinitis pigmentosa (RP) treatment. Dutasteride (DUT) is a 5α-reductase inhibitor that have not been associated with increases in serum testosterone levels. Furthermore, modulation or inhibition of 5α-reductase activity increases levels of neuroprotective steroids. We also studied the action mechanisms that provide DUT with a neuroprotective role in RP. To this end, the changes that dutasteride induce on markers of inflammation, and glutathione (GSH) metabolism in the retina of rds mice were studied.

Methods : Animals were treated in accordance with the ARVO statement for the use of animals in ophthalmic and vision research. Rds mice were treated intraperitoneally with DUT on postnatal days 11, 13, 15, 17 and 19 and euthanized on day 21. Hematoxylin-eosin, TUNEL, and rod and cone immunohistochemistry were performed to determine if DUT was able to delay photoreceptor death. Immunohistochemical techniques were used to study changes in retinal microglia (Iba-1) morphology and distribution. Degree of inflammatory cells activation was evaluated by measuring expression of CD68. Possible modifications of other glial cells were also studied with GFAP (glial fibrillar acid protein). Finally, GSH localization was examined, and western blot analysis was performed to determine retinal GSH synthesis and transport.

Results : DUT increased photoreceptor survival in rds mice. An increase in iba-1 positive cells was found in rds retinas and DUT normalized the number, migration and the length and number of branches in these cells (p<0,01). DUT decreased in CD68 and GFAP expression (more than 50% of increase in rds retina). Finally, DUT was also able to ameliorate the observed alterations in GSH metabolism in rds retina.

Conclusions : DUT may be used to ameliorate retinal micro and macroglial activation in RP, as well as alterations in the metabolism of the most important intracellular antioxidant.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×