Academic Journal

Minocycline and bone marrow-derived mononuclear cells as potential therapeutics for hereditary retinal degenerations.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Minocycline and bone marrow-derived mononuclear cells as potential therapeutics for hereditary retinal degenerations.
Συγγραφείς: 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.
Πηγή: Acta ophthalmologica [Acta Ophthalmol] 2026 Sep; Vol. 104 (6), pp. e671-e685. Date of Electronic Publication: 2026 Mar 10.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: 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
Ιατρικοί όροι (MeSH): 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
Περίληψη: 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.)
References: J Stem Cells. 2015;10(3):171-91. (PMID: 27125062)
Br J Ophthalmol. 2014 Mar;98(3):396-401. (PMID: 24326325)
Invest Ophthalmol Vis Sci. 2015 Jul;56(8):4487-98. (PMID: 26193926)
J Ophthalmic Vis Res. 2017 Jan-Mar;12(1):58-64. (PMID: 28299008)
Exp Eye Res. 2018 Feb;167:56-90. (PMID: 29122605)
Prog Retin Eye Res. 2014 May;40:1-15. (PMID: 24374240)
Arch Ophthalmol. 2012 May;130(5):629-34. (PMID: 22652848)
Invest Ophthalmol Vis Sci. 2008 Jan;49(1):442-52. (PMID: 18172124)
Int J Mol Sci. 2020 Sep 30;21(19):. (PMID: 33008136)
Int J Mol Sci. 2021 Dec 29;23(1):. (PMID: 35008772)
Graefes Arch Clin Exp Ophthalmol. 2009 Apr;247(4):503-14. (PMID: 19084985)
J Clin Invest. 2004 Sep;114(6):765-74. (PMID: 15372100)
Glia. 2011 Jul;59(7):1107-17. (PMID: 21547953)
Front Neuroanat. 2024 Feb 13;18:1335176. (PMID: 38415017)
Arch Ophthalmol. 1991 Jan;109(1):92-101. (PMID: 1987956)
Int J Mol Sci. 2017 Jul 28;18(8):. (PMID: 28788088)
Vision Res. 2004;44(21):2467-74. (PMID: 15358082)
Prog Retin Eye Res. 2015 May;46:31-66. (PMID: 25660226)
Exp Eye Res. 2014 Jan;118:135-44. (PMID: 24239509)
Stem Cell Res. 2015 Sep;15(2):387-94. (PMID: 26322852)
Invest Ophthalmol Vis Sci. 2018 Mar 1;59(3):1396-1409. (PMID: 29625463)
J Biomed Opt. 2023 Oct;28(10):106001. (PMID: 37841506)
PLoS One. 2015 Mar 20;10(3):e0120415. (PMID: 25793273)
Prog Retin Eye Res. 2017 Jan;56:148-165. (PMID: 27784628)
Eur J Pharmacol. 2007 Apr 10;560(2-3):142-9. (PMID: 17307159)
J Neuroinflammation. 2015 Nov 17;12:209. (PMID: 26576678)
Exp Eye Res. 2007 Sep;85(3):381-92. (PMID: 17662715)
Hum Mutat. 2018 Jul;39(7):887-913. (PMID: 29659094)
Neural Regen Res. 2019 Jul;14(7):1186-1190. (PMID: 30804243)
Prog Retin Eye Res. 2020 Mar;75:100779. (PMID: 31494256)
Prog Retin Eye Res. 2017 May;58:1-27. (PMID: 28111323)
J Comp Neurol. 2007 Jan 10;500(2):222-38. (PMID: 17111372)
Nat Genet. 2000 Nov;26(3):270-1. (PMID: 11062461)
J Neuroimmunol. 2018 Apr 15;317:95-99. (PMID: 29395319)
Stem Cell Investig. 2019 Sep 09;6:31. (PMID: 31620478)
J Neuroinflammation. 2012 Apr 02;9:62. (PMID: 22472085)
Invest Ophthalmol Vis Sci. 2016 Aug 1;57(10):4125-35. (PMID: 27537262)
Invest Ophthalmol Vis Sci. 1981 Nov;21(5):638-57. (PMID: 7028675)
Exp Eye Res. 2010 Dec;91(6):800-10. (PMID: 20955700)
Neural Regen Res. 2022 Sep;17(9):1937-1944. (PMID: 35142670)
J Neurosci. 2014 Jun 11;34(24):8139-50. (PMID: 24920619)
Brain Res. 2014 Oct 31;1587:54-68. (PMID: 25204691)
Cell Mol Neurobiol. 2023 Oct;43(7):3211-3250. (PMID: 37356043)
Stem Cell Rev Rep. 2019 Dec;15(6):880-891. (PMID: 31863334)
Biomed Res Int. 2016;2016:2954721. (PMID: 27294114)
Neural Regen Res. 2018 Nov;13(11):1885-1886. (PMID: 30233058)
Clin Ophthalmol. 2017 May 19;11:931-938. (PMID: 28579742)
Front Neuroanat. 2017 Mar 06;11:14. (PMID: 28321183)
Ophthalmic Genet. 2023 Feb;44(1):74-82. (PMID: 36036427)
Invest Ophthalmol Vis Sci. 2011 Nov 25;52(12):9124-30. (PMID: 22039242)
Graefes Arch Clin Exp Ophthalmol. 2017 Aug;255(8):1581-1592. (PMID: 28523456)
Br J Pharmacol. 2013 May;169(2):337-52. (PMID: 23441623)
Neurochem Int. 2005 Jul;47(1-2):152-8. (PMID: 15904993)
Prog Retin Eye Res. 2016 Mar;51:1-40. (PMID: 26113209)
Prog Retin Eye Res. 2019 Mar;69:1-37. (PMID: 30445193)
Stroke. 2016 Jun;47(6):1632-9. (PMID: 27165959)
Invest Ophthalmol Vis Sci. 2018 Sep 4;59(11):4392-4403. (PMID: 30193320)
Eur J Neurosci. 2005 Sep;22(5):1057-72. (PMID: 16176347)
Adv Exp Med Biol. 2016;854:571-7. (PMID: 26427461)
Invest Ophthalmol Vis Sci. 2010 Jul;51(7):3742-8. (PMID: 20207980)
Mol Vis. 2007 Jul 09;13:1073-82. (PMID: 17653052)
Lancet. 2006 Nov 18;368(9549):1795-809. (PMID: 17113430)
Annu Rev Vis Sci. 2018 Sep 15;4:45-77. (PMID: 29852094)
J Neurosci. 2002 Mar 1;22(5):1763-71. (PMID: 11880505)
Stem Cells. 2002;20(4):279-83. (PMID: 12110696)
J Neuroinflammation. 2014 Oct 29;11:186. (PMID: 25359524)
Sci Rep. 2018 Jan 31;8(1):1968. (PMID: 29386551)
Neurodegener Dis. 2012;9(4):187-98. (PMID: 22584394)
Stem Cell Investig. 2018 Jun 06;5:18. (PMID: 30050918)
Exp Eye Res. 2020 Jan;190:107865. (PMID: 31682846)
Acta Ophthalmol. 2026 Sep;104(6):e671-e685. (PMID: 41808280)
Int J Mol Sci. 2019 Jan 28;20(3):. (PMID: 30696106)
Invest Ophthalmol Vis Sci. 2008 Apr;49(4):1437-46. (PMID: 18385061)
Clin Ophthalmol. 2022 Jun 20;16:1993-2010. (PMID: 35757022)
Br J Ophthalmol. 2018 May;102(5):575-585. (PMID: 29545417)
Invest Ophthalmol Vis Sci. 2016 Sep 1;57(11):4692-703. (PMID: 27607415)
Biomed Res Int. 2019 Oct 30;2019:8276140. (PMID: 31781647)
Exp Eye Res. 2019 Nov;188:107781. (PMID: 31473259)
Prog Retin Eye Res. 2019 Jul;71:1-25. (PMID: 30885665)
Invest Ophthalmol Vis Sci. 2020 Mar 9;61(3):47. (PMID: 32232352)
Exp Eye Res. 2010 Sep;91(3):449-55. (PMID: 20603115)
Redox Biol. 2022 Nov;57:102506. (PMID: 36270186)
Acta Ophthalmol. 2022 Sep;100(6):e1313-e1331. (PMID: 35514078)
Prog Retin Eye Res. 2018 Mar;63:107-131. (PMID: 29097191)
Clin Interv Aging. 2013;8:1089-95. (PMID: 23983461)
Am J Ophthalmol. 2017 May;177:169-174. (PMID: 28237413)
Lancet Glob Health. 2017 Dec;5(12):e1221-e1234. (PMID: 29032195)
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
Βάση Δεδομένων: MEDLINE