Academic Journal
Minocycline and bone marrow-derived mononuclear cells as potential therapeutics for hereditary retinal degenerations.
| Title: | Minocycline and bone marrow-derived mononuclear cells as potential therapeutics for hereditary retinal degenerations. |
|---|---|
| Authors: | Videla-Ristol A; Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain.; Instituto Murciano de Investigación Biosanitaria-Virgen de la Arrixaca Pascual Parrilla (IMIB-Arrixaca), Murcia, Spain., Martínez-Vacas A; Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain.; Instituto Murciano de Investigación Biosanitaria-Virgen de la Arrixaca Pascual Parrilla (IMIB-Arrixaca), Murcia, Spain., García-Bernal D; Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain.; Instituto Murciano de Investigación Biosanitaria-Virgen de la Arrixaca Pascual Parrilla (IMIB-Arrixaca), Murcia, Spain.; Departamento de Bioquímica, Biología Molecular B e Inmunología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain., Vidal-Sanz M; Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain.; Instituto Murciano de Investigación Biosanitaria-Virgen de la Arrixaca Pascual Parrilla (IMIB-Arrixaca), Murcia, Spain., Villegas-Pérez MP; Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain.; Instituto Murciano de Investigación Biosanitaria-Virgen de la Arrixaca Pascual Parrilla (IMIB-Arrixaca), Murcia, Spain., García-Ayuso D; Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain.; Instituto Murciano de Investigación Biosanitaria-Virgen de la Arrixaca Pascual Parrilla (IMIB-Arrixaca), Murcia, Spain., Di Pierdomenico J; Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain.; Instituto Murciano de Investigación Biosanitaria-Virgen de la Arrixaca Pascual Parrilla (IMIB-Arrixaca), Murcia, Spain. |
| Source: | Acta ophthalmologica [Acta Ophthalmol] 2026 Sep; Vol. 104 (6), pp. e671-e685. Date of Electronic Publication: 2026 Mar 10. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101468102 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1755-3768 (Electronic) Linking ISSN: 1755375X NLM ISO Abbreviation: Acta Ophthalmol Subsets: MEDLINE |
| Imprint Name(s): | Publication: Oxford, UK : Wiley-Blackwell Original Publication: Oxford, UK ; Malden, MA : Blackwell Munksgaard |
| MeSH Terms: | Minocycline*/administration & dosage , Minocycline*/therapeutic use , Retinal Degeneration*/therapy , Retinal Degeneration*/diagnosis , Bone Marrow Transplantation*/methods, Anti-Bacterial Agents/administration & dosage ; Animals ; Rats ; Disease Models, Animal ; Tomography, Optical Coherence ; Intravitreal Injections ; Rats, Mutant Strains |
| Abstract: | Purpose: To assess in Royal College of Surgeons (RCS) rats if the combination of two previously documented neuroprotective strategies: minocycline administration and bone marrow-derived mononuclear cells (BM-MNCs) intravitreal transplantation, offers enhanced neuroprotection compared with each treatment alone. Methods: Forty-eight homozygous pigmented RCS rats were divided into four groups: control, intravitreal BM-MNC transplantation, systemic minocycline treatment or combined therapy. Treatments were administered at postnatal day (P) 27-28. Animals were evaluated in vivo by spectral domain optical coherence tomography (SD-OCT) at P28, P35 and P51. Retinal sections were analysed for photoreceptor survival (outer nuclear layer [ONL] cell counts), synaptic preservation (Bassoon immunoreactivity), microglial activation (Iba-1+ cells) and macroglial reactivity (glial fibrillary acidic protein [GFAP] expression). Results: Both BM-MNC and minocycline monotherapies significantly preserved total and outer retinal thicknesses and increased ONL nuclei counts compared with controls. Combined treatment yielded superior protection at both P35 and P51. Minocycline alone or in combination significantly reduced microglial cell activation, while BM-MNCs alone or in combination significantly reduced GFAP expression. Synaptic integrity in the outer plexiform layer, assessed via Bassoon labelling, was significantly better preserved in treated animals, with the highest levels observed in the combined therapy group. Conclusions: Minocycline and BM-MNCs provide complementary neuroprotective effects in the RCS rat model. While minocycline reduces microglial activation, BM-MNCs modulate macroglial response. Their combination enhances photoreceptor survival and synaptic preservation more effectively than either treatment alone. These findings support the therapeutic potential of combining pharmacological and cell-based interventions in hereditary retinal degenerations. (© 2026 The Author(s). Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.) |
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| Grant Information: | PI19/00203 Instituto de Salud Carlos III; PI22/00900 Instituto de Salud Carlos III; RD16/0008/0026 Instituto de Salud Carlos III; Grant/Award Number: PID2023-151006OB-I00/AEI/10.13039/501100011033/FEDER, UE MCIN/AEI; RD21/0002/0014 NextGenerationEU; RED2018-102499-T NextGenerationEU; NEUBIRET23037/GERM/25 FUNDACION SÉNECA - AGENCIA DE CIENCIA Y TECNOLOGÍA DE LA REGIÓN DE MURCIA - GERM (Ayudas a Grupos de Investigación de Excelencia de la Región de Murcia); PI25/00206 Instituto de Salud Carlos III |
| Contributed Indexing: | Keywords: RCS rat; bone marrow–derived mononuclear cells; glial activation; minocycline; photoreceptor neuroprotection; retinal degeneration |
| Substance Nomenclature: | FYY3R43WGO (Minocycline) 0 (Anti-Bacterial Agents) |
| Entry Date(s): | Date Created: 20260311 Date Completed: 20260811 Latest Revision: 20260813 |
| Update Code: | 20260813 |
| PubMed Central ID: | PMC13460373 |
| DOI: | 10.1111/aos.70108 |
| PMID: | 41808280 |
| Database: | MEDLINE |
| FullText | Text: Availability: 0 CustomLinks: – Url: https://resolver.ebsco.com/c/fiv2js/result?sid=EBSCO:cmedm&genre=article&issn=17553768&ISBN=&volume=104&issue=6&date=20260901&spage=e671&pages=e671-e685&title=Acta ophthalmologica&atitle=Minocycline%20and%20bone%20marrow-derived%20mononuclear%20cells%20as%20potential%20therapeutics%20for%20hereditary%20retinal%20degenerations.&aulast=Videla-Ristol%20A&id=DOI:10.1111/aos.70108 Name: Full Text Finder (for New FTF UI) (ns324271) Category: fullText Text: Full Text Finder MouseOverText: Full Text Finder |
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| Header | DbId: cmedm DbLabel: MEDLINE An: 41808280 AccessLevel: 3 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Minocycline and bone marrow-derived mononuclear cells as potential therapeutics for hereditary retinal degenerations. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AU" term="%22Videla-Ristol+A%22">Videla-Ristol A</searchLink>; Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain.; Instituto Murciano de Investigación Biosanitaria-Virgen de la Arrixaca Pascual Parrilla (IMIB-Arrixaca), Murcia, Spain.<br /><searchLink fieldCode="AU" term="%22Martínez-Vacas+A%22">Martínez-Vacas A</searchLink>; Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain.; Instituto Murciano de Investigación Biosanitaria-Virgen de la Arrixaca Pascual Parrilla (IMIB-Arrixaca), Murcia, Spain.<br /><searchLink fieldCode="AU" term="%22García-Bernal+D%22">García-Bernal D</searchLink>; Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain.; Instituto Murciano de Investigación Biosanitaria-Virgen de la Arrixaca Pascual Parrilla (IMIB-Arrixaca), Murcia, Spain.; Departamento de Bioquímica, Biología Molecular B e Inmunología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain.<br /><searchLink fieldCode="AU" term="%22Vidal-Sanz+M%22">Vidal-Sanz M</searchLink>; Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain.; Instituto Murciano de Investigación Biosanitaria-Virgen de la Arrixaca Pascual Parrilla (IMIB-Arrixaca), Murcia, Spain.<br /><searchLink fieldCode="AU" term="%22Villegas-Pérez+MP%22">Villegas-Pérez MP</searchLink>; Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain.; Instituto Murciano de Investigación Biosanitaria-Virgen de la Arrixaca Pascual Parrilla (IMIB-Arrixaca), Murcia, Spain.<br /><searchLink fieldCode="AU" term="%22García-Ayuso+D%22">García-Ayuso D</searchLink>; Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain.; Instituto Murciano de Investigación Biosanitaria-Virgen de la Arrixaca Pascual Parrilla (IMIB-Arrixaca), Murcia, Spain.<br /><searchLink fieldCode="AU" term="%22Di+Pierdomenico+J%22">Di Pierdomenico J</searchLink>; Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain.; Instituto Murciano de Investigación Biosanitaria-Virgen de la Arrixaca Pascual Parrilla (IMIB-Arrixaca), Murcia, Spain. – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22101468102%22">Acta ophthalmologica</searchLink> [Acta Ophthalmol] 2026 Sep; Vol. 104 (6), pp. e671-e685. <i>Date of Electronic Publication: </i>2026 Mar 10. – Name: TypePub Label: Publication Type Group: TypPub Data: Journal Article – Name: Language Label: Language Group: Lang Data: English – Name: TitleSource Label: Journal Info Group: Src Data: <i>Publisher: </i><searchLink fieldCode="PB" term="%22Wiley-Blackwell%22">Wiley-Blackwell </searchLink><i>Country of Publication: </i>England <i>NLM ID: </i>101468102 <i>Publication Model: </i>Print-Electronic <i>Cited Medium: </i>Internet <i>ISSN: </i>1755-3768 (Electronic) <i>Linking ISSN: </i><searchLink fieldCode="IS" term="%221755375X%22">1755375X </searchLink><i>NLM ISO Abbreviation: </i>Acta Ophthalmol <i>Subsets: </i>MEDLINE – Name: PublisherInfo Label: Imprint Name(s) Group: PubInfo Data: <i>Publication</i>: Oxford, UK : Wiley-Blackwell<br /><i>Original Publication</i>: Oxford, UK ; Malden, MA : Blackwell Munksgaard – Name: SubjectMESH Label: MeSH Terms Group: Su Data: <searchLink fieldCode="MM" term="%22Minocycline%22">Minocycline*</searchLink>/<searchLink fieldCode="MM" term="%22Minocycline+administration+%26+dosage%22">administration & dosage</searchLink> <br /><searchLink fieldCode="MM" term="%22Minocycline%22">Minocycline*</searchLink>/<searchLink fieldCode="MM" term="%22Minocycline+therapeutic+use%22">therapeutic use</searchLink> <br /><searchLink fieldCode="MM" term="%22Retinal+Degeneration%22">Retinal Degeneration*</searchLink>/<searchLink fieldCode="MM" term="%22Retinal+Degeneration+therapy%22">therapy</searchLink> <br /><searchLink fieldCode="MM" term="%22Retinal+Degeneration%22">Retinal Degeneration*</searchLink>/<searchLink fieldCode="MM" term="%22Retinal+Degeneration+diagnosis%22">diagnosis</searchLink> <br /><searchLink fieldCode="MM" term="%22Bone+Marrow+Transplantation%22">Bone Marrow Transplantation*</searchLink>/<searchLink fieldCode="MM" term="%22Bone+Marrow+Transplantation+methods%22">methods</searchLink><br /><searchLink fieldCode="MH" term="%22Anti-Bacterial+Agents%22">Anti-Bacterial Agents</searchLink>/<searchLink fieldCode="MH" term="%22Anti-Bacterial+Agents+administration+%26+dosage%22">administration & dosage</searchLink> ; <searchLink fieldCode="MH" term="%22Animals%22">Animals</searchLink> ; <searchLink fieldCode="MH" term="%22Rats%22">Rats</searchLink> ; <searchLink fieldCode="MH" term="%22Disease+Models%2C+Animal%22">Disease Models, Animal</searchLink> ; <searchLink fieldCode="MH" term="%22Tomography%2C+Optical+Coherence%22">Tomography, Optical Coherence</searchLink> ; <searchLink fieldCode="MH" term="%22Intravitreal+Injections%22">Intravitreal Injections</searchLink> ; <searchLink fieldCode="MH" term="%22Rats%2C+Mutant+Strains%22">Rats, Mutant Strains</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Purpose: To assess in Royal College of Surgeons (RCS) rats if the combination of two previously documented neuroprotective strategies: minocycline administration and bone marrow-derived mononuclear cells (BM-MNCs) intravitreal transplantation, offers enhanced neuroprotection compared with each treatment alone.<br />Methods: Forty-eight homozygous pigmented RCS rats were divided into four groups: control, intravitreal BM-MNC transplantation, systemic minocycline treatment or combined therapy. Treatments were administered at postnatal day (P) 27-28. Animals were evaluated in vivo by spectral domain optical coherence tomography (SD-OCT) at P28, P35 and P51. Retinal sections were analysed for photoreceptor survival (outer nuclear layer [ONL] cell counts), synaptic preservation (Bassoon immunoreactivity), microglial activation (Iba-1+ cells) and macroglial reactivity (glial fibrillary acidic protein [GFAP] expression).<br />Results: Both BM-MNC and minocycline monotherapies significantly preserved total and outer retinal thicknesses and increased ONL nuclei counts compared with controls. Combined treatment yielded superior protection at both P35 and P51. Minocycline alone or in combination significantly reduced microglial cell activation, while BM-MNCs alone or in combination significantly reduced GFAP expression. Synaptic integrity in the outer plexiform layer, assessed via Bassoon labelling, was significantly better preserved in treated animals, with the highest levels observed in the combined therapy group.<br />Conclusions: Minocycline and BM-MNCs provide complementary neuroprotective effects in the RCS rat model. While minocycline reduces microglial activation, BM-MNCs modulate macroglial response. Their combination enhances photoreceptor survival and synaptic preservation more effectively than either treatment alone. These findings support the therapeutic potential of combining pharmacological and cell-based interventions in hereditary retinal degenerations.<br /> (© 2026 The Author(s). Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.) – Name: Ref Label: References Group: RefInfo Data: J Stem Cells. 2015;10(3):171-91. (PMID: <searchLink fieldCode="PM" term="%2227125062%22">27125062)</searchLink><br />Br J Ophthalmol. 2014 Mar;98(3):396-401. (PMID: <searchLink fieldCode="PM" term="%2224326325%22">24326325)</searchLink><br />Invest Ophthalmol Vis Sci. 2015 Jul;56(8):4487-98. (PMID: <searchLink fieldCode="PM" term="%2226193926%22">26193926)</searchLink><br />J Ophthalmic Vis Res. 2017 Jan-Mar;12(1):58-64. (PMID: <searchLink fieldCode="PM" term="%2228299008%22">28299008)</searchLink><br />Exp Eye Res. 2018 Feb;167:56-90. (PMID: <searchLink fieldCode="PM" term="%2229122605%22">29122605)</searchLink><br />Prog Retin Eye Res. 2014 May;40:1-15. (PMID: <searchLink fieldCode="PM" term="%2224374240%22">24374240)</searchLink><br />Arch Ophthalmol. 2012 May;130(5):629-34. (PMID: <searchLink fieldCode="PM" term="%2222652848%22">22652848)</searchLink><br />Invest Ophthalmol Vis Sci. 2008 Jan;49(1):442-52. (PMID: <searchLink fieldCode="PM" term="%2218172124%22">18172124)</searchLink><br />Int J Mol Sci. 2020 Sep 30;21(19):. (PMID: <searchLink fieldCode="PM" term="%2233008136%22">33008136)</searchLink><br />Int J Mol Sci. 2021 Dec 29;23(1):. (PMID: <searchLink fieldCode="PM" term="%2235008772%22">35008772)</searchLink><br />Graefes Arch Clin Exp Ophthalmol. 2009 Apr;247(4):503-14. (PMID: <searchLink fieldCode="PM" term="%2219084985%22">19084985)</searchLink><br />J Clin Invest. 2004 Sep;114(6):765-74. (PMID: <searchLink fieldCode="PM" term="%2215372100%22">15372100)</searchLink><br />Glia. 2011 Jul;59(7):1107-17. (PMID: <searchLink fieldCode="PM" term="%2221547953%22">21547953)</searchLink><br />Front Neuroanat. 2024 Feb 13;18:1335176. (PMID: <searchLink fieldCode="PM" term="%2238415017%22">38415017)</searchLink><br />Arch Ophthalmol. 1991 Jan;109(1):92-101. (PMID: <searchLink fieldCode="PM" term="%221987956%22">1987956)</searchLink><br />Int J Mol Sci. 2017 Jul 28;18(8):. (PMID: <searchLink fieldCode="PM" term="%2228788088%22">28788088)</searchLink><br />Vision Res. 2004;44(21):2467-74. (PMID: <searchLink fieldCode="PM" term="%2215358082%22">15358082)</searchLink><br />Prog Retin Eye Res. 2015 May;46:31-66. (PMID: <searchLink fieldCode="PM" term="%2225660226%22">25660226)</searchLink><br />Exp Eye Res. 2014 Jan;118:135-44. (PMID: <searchLink fieldCode="PM" term="%2224239509%22">24239509)</searchLink><br />Stem Cell Res. 2015 Sep;15(2):387-94. (PMID: <searchLink fieldCode="PM" term="%2226322852%22">26322852)</searchLink><br />Invest Ophthalmol Vis Sci. 2018 Mar 1;59(3):1396-1409. (PMID: <searchLink fieldCode="PM" term="%2229625463%22">29625463)</searchLink><br />J Biomed Opt. 2023 Oct;28(10):106001. (PMID: <searchLink fieldCode="PM" term="%2237841506%22">37841506)</searchLink><br />PLoS One. 2015 Mar 20;10(3):e0120415. (PMID: <searchLink fieldCode="PM" term="%2225793273%22">25793273)</searchLink><br />Prog Retin Eye Res. 2017 Jan;56:148-165. 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(PMID: <searchLink fieldCode="PM" term="%2229032195%22">29032195)</searchLink> – Name: GrantInfo Label: Grant Information Group: Grant Data: PI19/00203 Instituto de Salud Carlos III; PI22/00900 Instituto de Salud Carlos III; RD16/0008/0026 Instituto de Salud Carlos III; Grant/Award Number: PID2023-151006OB-I00/AEI/10.13039/501100011033/FEDER, UE MCIN/AEI; RD21/0002/0014 NextGenerationEU; RED2018-102499-T NextGenerationEU; NEUBIRET23037/GERM/25 FUNDACION SÉNECA - AGENCIA DE CIENCIA Y TECNOLOGÍA DE LA REGIÓN DE MURCIA - GERM (Ayudas a Grupos de Investigación de Excelencia de la Región de Murcia); PI25/00206 Instituto de Salud Carlos III – Name: SubjectMinor Label: Contributed Indexing Group: Data: <i>Keywords: </i>RCS rat; bone marrow–derived mononuclear cells; glial activation; minocycline; photoreceptor neuroprotection; retinal degeneration – Name: NumberCAS Label: Substance Nomenclature Group: ID Data: FYY3R43WGO (Minocycline)<br />0 (Anti-Bacterial Agents) – Name: DateEntry Label: Entry Date(s) Group: Date Data: <i>Date Created: </i>20260311 <i>Date Completed: </i>20260811 <i>Latest Revision: </i>20260813 – Name: DateUpdate Label: Update Code Group: Date Data: 20260813 – Name: PubmedCentralID Label: PubMed Central ID Group: ID Data: PMC13460373 – Name: DOI Label: DOI Group: ID Data: 10.1111/aos.70108 – Name: AN Label: PMID Group: ID Data: 41808280 |
| PLink | https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=cmedm&AN=41808280 |
| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1111/aos.70108 Languages: – Code: eng Text: English PhysicalDescription: Pagination: StartPage: e671 Subjects: – SubjectFull: Anti-Bacterial Agents administration & dosage Type: general – SubjectFull: Animals Type: general – SubjectFull: Rats Type: general – SubjectFull: Disease Models, Animal Type: general – SubjectFull: Tomography, Optical Coherence Type: general – SubjectFull: Intravitreal Injections Type: general – SubjectFull: Rats, Mutant Strains Type: general – SubjectFull: Minocycline administration & dosage Type: general – SubjectFull: Minocycline therapeutic use Type: general – SubjectFull: Retinal Degeneration therapy Type: general – SubjectFull: Retinal Degeneration diagnosis Type: general – SubjectFull: Bone Marrow Transplantation methods Type: general Titles: – TitleFull: Minocycline and bone marrow-derived mononuclear cells as potential therapeutics for hereditary retinal degenerations. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Videla-Ristol A – PersonEntity: Name: NameFull: Martínez-Vacas A – PersonEntity: Name: NameFull: García-Bernal D – PersonEntity: Name: NameFull: Vidal-Sanz M – PersonEntity: Name: NameFull: Villegas-Pérez MP – PersonEntity: Name: NameFull: García-Ayuso D – PersonEntity: Name: NameFull: Di Pierdomenico J IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 09 Text: 2026 Sep Type: published Y: 2026 Identifiers: – Type: issn-electronic Value: 1755-3768 Numbering: – Type: volume Value: 104 – Type: issue Value: 6 Titles: – TitleFull: Acta ophthalmologica Type: main |
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