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This research was funded by the Research Network RETIBRAIN (RED2018-102499-T) of the Spanish Ministry of Science and Innovation, and the Spanish Ministry of Science and Innovation Ref. RTI2018-095793-B-I00 and Ref. PID2021-125986OB-I00. J.A.F.-A. is currently supported by a Predoctoral Fellowship (FPU17/01023) from the Spanish Ministry of Science, Innovation, and Universities. E.d.S. is currently supported by a Predoctoral Fellowship (FPU18/00630) from the Spanish Ministry of Science, Innovation, and Universities. I.L.-C. is currently supported by a Predoctoral Fellowship (CT42/18-CT43/18) from the Complutense University of Madrid. L.S.-P. is currently supported by a Predoctoral Fellowship (CT82/20-CT83/20) from the Complutense University of Madrid. The sponsor or funding organization had no role in the design or conduct of this research.

Analysis of institutional authors

Salobrar-García, ElenaAuthorFernandez-Mendivil, CristinaAuthorDel Sastre, EricAuthor
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Article

Microglial Hemoxygenase-1 Deletion Reduces Inflammation in the Retina of Old Mice with Tauopathy

Publicated to:Antioxidants. 11 (11): 2151- - 2022-11-01 11(11), DOI: 10.3390/antiox11112151

Authors: Fernandez-Albarral, Jose A; Salobrar-Garcia, Elena; Matamoros, Jose A; Fernandez-Mendivil, Cristina; del Sastre, Eric; Chen, Lejing; de Hoz, Rosa; Lopez-Cuenca, Ines; Sanchez-Puebla, Lidia; Ramirez, Jose M; Salazar, Juan J; Lopez, Manuela G; Ramirez, Ana, I

Affiliations

Hosp Univ La Princesa, Inst Invest Sanitario IIS IP, Madrid 28006, Spain - Author
Univ Autonoma Madrid, Sch Med, Inst Teofilo Hernando Drug Discovery, Dept Pharmacol, Madrid 28029, Spain - Author
Univ Complutense Madrid, Fac Med, Dept Inmunol Oftalmol & ORL, Madrid 28040, Spain - Author
Univ Complutense Madrid, Fac Opt & Optometria, Dept Inmunol Oftalmol & ORL, Madrid 28037, Spain - Author
Univ Complutense Madrid, Inst Invest Oftalmol Ramon Castroviejo, IdISSC, Grp UCM 920105, Madrid 28040, Spain - Author
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Abstract

Tauopathies such as Alzheimer's disease are characterized by the accumulation of neurotoxic aggregates of tau protein. With aging and, especially, in Alzheimer's patients, the inducible enzyme heme oxygenase 1 (HO-1) progressively increases in microglia, causing iron accumulation, neuroinflammation, and neurodegeneration. The retina is an organ that can be readily accessed and can reflect changes that occur in the brain. In this context, we evaluated how the lack of microglial HO-1, using mice that do not express HO-1 in microglia (HMO-KO), impacts retinal macro and microgliosis of aged subjects (18 months old mice) subjected to tauopathy by intrahippocampal delivery of AAV-hTau(P301L) (TAU). Our results show that although tauopathy, measured as anti-TAUY9 and anti-AT8 positive immunostaining, was not observed in the retina of WT-TAU or HMO-KO+TAU mice, a morphometric study of retinal microglia and macroglia showed significant retinal changes in the TAU group compared to the WT group, such as: (i) increased number of activated microglia, (ii) retraction of microglial processes, (iii) increased number of CD68+ microglia, and (iv) increased retinal area occupied by GFAP (AROA) and C3 (AROC3). This retinal inflammatory profile was reduced in HMO-KO+TAU mice. Conclusion: Reduction of microglial HO-1 could be beneficial to prevent tauopathy-induced neuroinflammation.

Keywords
heme oxygenase 1 (ho-1)macrogliamicroglianeurodegenerative diseasesneuroinflammationretinaAccumulationAlzheimersAstrocytesBrainDiseaseDystrophic microgliaHeme oxygenase 1Heme oxygenase 1 (ho-1)MacrogliaMicrogliaNeurodegenerationNeurodegenerative diseasesNeuroinflammationRetinaTau pathologyTauopathies

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Antioxidants due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2022, it was in position 6/60, thus managing to position itself as a Q1 (Primer Cuartil), in the category Food Science & Technology. Notably, the journal is positioned above the 90th percentile.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 1.15, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions May 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-05-23, the following number of citations:

  • WoS: 1
  • Scopus: 2
  • OpenCitations: 1
Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-05-23:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 44.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 44 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 5.2.
  • The number of mentions on the social network X (formerly Twitter): 6 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
Leadership analysis of institutional authors

the author responsible for correspondence tasks has been Lopez, Manuela G.