Effects of minocycline and tetracycline on retinal ganglion cell survival after axotomy

D. C. Baptiste; K. J. Powell; C. A.B. Jollimore; C. Hamilton; T. L. LeVatte; M. L. Archibald; B. C. Chauhan; G. S. Robertson; M. E.M. Kelly

doi:10.1016/j.neuroscience.2005.04.011

Effects of minocycline and tetracycline on retinal ganglion cell survival after axotomy

D. C. Baptiste, K. J. Powell, C. A.B. Jollimore, C. Hamilton, T. L. LeVatte, M. L. Archibald, B. C. Chauhan, G. S. Robertson, M. E.M. Kelly

Medicine

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55 Citas (Scopus)

Resumen

In the present study, we compared the in vivo neuroprotective efficacy of intraperitoneally administered tetracycline and minocycline to enhance the survival of retinal ganglion cells (RGCs) following unilateral axotomy of the adult rat optic nerve. We also examined the effects of the tetracycline drugs on the activation of retinal microglia. RGCs in retinal whole-mounts were visualized by retrograde labeling with fluorogold. The presence of activated microglia was confirmed immunohistochemically using OX-42 monoclonal antibodies. Optic nerve axotomy produced RGC death and increased activation of microglia. No significant RGC loss was seen prior to 5 days and approximately 50% and 80-90% cell loss occurred at 7 and 14 days, respectively. Examination of the effects of tetracycline and minocycline on RGC survival at 7 days post-axotomy, revealed increased numbers of RGCs in minocycline-treated animals (75% of non-axotomized control) compared with vehicle-only (52% of control) and tetracycline-treated (58% of control) animals. The densities of RGCs (RGCs/mm²±S.D.) for control, vehicle-, tetracycline- and minocycline-treated axotomized animals were 1996±81, 1029±186, 1158±190 and 1497±312, respectively. The neuroprotective effect of minocycline seen at 7 days was transient, since RGCs present in minocycline-treated animals at 14 days post-axotomy (281±43, 14% of control) were not significantly different to vehicle-treated animals (225±47, 11% of control). OX-42 staining of activated retinal microglia was reduced in tetracycline- and minocycline-treated axotomized animals compared with axotomized animals receiving vehicle-only. These results demonstrate that systemic administration of the second-generation tetracycline derivative, minocycline, delays the death of axotomized RGCs by a mechanism that may be associated with inhibition of microglia activation. The neuroprotective efficacy of minocycline following optic nerve axotomy was superior to that of tetracycline.

Idioma original	English
Páginas (desde-hasta)	575-582
Número de páginas	8
Publicación	Neuroscience
Volumen	134
N.º	2
DOI	https://doi.org/10.1016/j.neuroscience.2005.04.011
Estado	Published - 2005

Nota bibliográfica

Funding Information:
This work was supported by grants from the Glaucoma Research Society of Canada (M.E.M.K., K.J.P.), and grants, IAO-13484 (M.E.M.K.) and MOP-57851 (B.C.C.) from the Canadian Institutes of Health Research (CIHR). D.C.B. was funded by a J. R. Johnston Studentship award, K.J.P. was funded by a CIHR/INMHA/Estate of Betty Irene West Fellowship award and G.S.R. is supported by a CIHR-RxandD Chair.

ASJC Scopus Subject Areas

General Neuroscience

PubMed: MeSH publication types

Journal Article
Research Support, Non-U.S. Gov't

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10.1016/j.neuroscience.2005.04.011

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title = "Effects of minocycline and tetracycline on retinal ganglion cell survival after axotomy",

abstract = "In the present study, we compared the in vivo neuroprotective efficacy of intraperitoneally administered tetracycline and minocycline to enhance the survival of retinal ganglion cells (RGCs) following unilateral axotomy of the adult rat optic nerve. We also examined the effects of the tetracycline drugs on the activation of retinal microglia. RGCs in retinal whole-mounts were visualized by retrograde labeling with fluorogold. The presence of activated microglia was confirmed immunohistochemically using OX-42 monoclonal antibodies. Optic nerve axotomy produced RGC death and increased activation of microglia. No significant RGC loss was seen prior to 5 days and approximately 50% and 80-90% cell loss occurred at 7 and 14 days, respectively. Examination of the effects of tetracycline and minocycline on RGC survival at 7 days post-axotomy, revealed increased numbers of RGCs in minocycline-treated animals (75% of non-axotomized control) compared with vehicle-only (52% of control) and tetracycline-treated (58% of control) animals. The densities of RGCs (RGCs/mm2±S.D.) for control, vehicle-, tetracycline- and minocycline-treated axotomized animals were 1996±81, 1029±186, 1158±190 and 1497±312, respectively. The neuroprotective effect of minocycline seen at 7 days was transient, since RGCs present in minocycline-treated animals at 14 days post-axotomy (281±43, 14% of control) were not significantly different to vehicle-treated animals (225±47, 11% of control). OX-42 staining of activated retinal microglia was reduced in tetracycline- and minocycline-treated axotomized animals compared with axotomized animals receiving vehicle-only. These results demonstrate that systemic administration of the second-generation tetracycline derivative, minocycline, delays the death of axotomized RGCs by a mechanism that may be associated with inhibition of microglia activation. The neuroprotective efficacy of minocycline following optic nerve axotomy was superior to that of tetracycline.",

author = "Baptiste, {D. C.} and Powell, {K. J.} and Jollimore, {C. A.B.} and C. Hamilton and LeVatte, {T. L.} and Archibald, {M. L.} and Chauhan, {B. C.} and Robertson, {G. S.} and Kelly, {M. E.M.}",

note = "Funding Information: This work was supported by grants from the Glaucoma Research Society of Canada (M.E.M.K., K.J.P.), and grants, IAO-13484 (M.E.M.K.) and MOP-57851 (B.C.C.) from the Canadian Institutes of Health Research (CIHR). D.C.B. was funded by a J. R. Johnston Studentship award, K.J.P. was funded by a CIHR/INMHA/Estate of Betty Irene West Fellowship award and G.S.R. is supported by a CIHR-RxandD Chair.",

year = "2005",

doi = "10.1016/j.neuroscience.2005.04.011",

language = "English",

volume = "134",

pages = "575--582",

journal = "Neuroscience",

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T1 - Effects of minocycline and tetracycline on retinal ganglion cell survival after axotomy

AU - Baptiste, D. C.

AU - Powell, K. J.

AU - Jollimore, C. A.B.

AU - Hamilton, C.

AU - LeVatte, T. L.

AU - Archibald, M. L.

AU - Chauhan, B. C.

AU - Robertson, G. S.

AU - Kelly, M. E.M.

N1 - Funding Information: This work was supported by grants from the Glaucoma Research Society of Canada (M.E.M.K., K.J.P.), and grants, IAO-13484 (M.E.M.K.) and MOP-57851 (B.C.C.) from the Canadian Institutes of Health Research (CIHR). D.C.B. was funded by a J. R. Johnston Studentship award, K.J.P. was funded by a CIHR/INMHA/Estate of Betty Irene West Fellowship award and G.S.R. is supported by a CIHR-RxandD Chair.

PY - 2005

Y1 - 2005

N2 - In the present study, we compared the in vivo neuroprotective efficacy of intraperitoneally administered tetracycline and minocycline to enhance the survival of retinal ganglion cells (RGCs) following unilateral axotomy of the adult rat optic nerve. We also examined the effects of the tetracycline drugs on the activation of retinal microglia. RGCs in retinal whole-mounts were visualized by retrograde labeling with fluorogold. The presence of activated microglia was confirmed immunohistochemically using OX-42 monoclonal antibodies. Optic nerve axotomy produced RGC death and increased activation of microglia. No significant RGC loss was seen prior to 5 days and approximately 50% and 80-90% cell loss occurred at 7 and 14 days, respectively. Examination of the effects of tetracycline and minocycline on RGC survival at 7 days post-axotomy, revealed increased numbers of RGCs in minocycline-treated animals (75% of non-axotomized control) compared with vehicle-only (52% of control) and tetracycline-treated (58% of control) animals. The densities of RGCs (RGCs/mm2±S.D.) for control, vehicle-, tetracycline- and minocycline-treated axotomized animals were 1996±81, 1029±186, 1158±190 and 1497±312, respectively. The neuroprotective effect of minocycline seen at 7 days was transient, since RGCs present in minocycline-treated animals at 14 days post-axotomy (281±43, 14% of control) were not significantly different to vehicle-treated animals (225±47, 11% of control). OX-42 staining of activated retinal microglia was reduced in tetracycline- and minocycline-treated axotomized animals compared with axotomized animals receiving vehicle-only. These results demonstrate that systemic administration of the second-generation tetracycline derivative, minocycline, delays the death of axotomized RGCs by a mechanism that may be associated with inhibition of microglia activation. The neuroprotective efficacy of minocycline following optic nerve axotomy was superior to that of tetracycline.

AB - In the present study, we compared the in vivo neuroprotective efficacy of intraperitoneally administered tetracycline and minocycline to enhance the survival of retinal ganglion cells (RGCs) following unilateral axotomy of the adult rat optic nerve. We also examined the effects of the tetracycline drugs on the activation of retinal microglia. RGCs in retinal whole-mounts were visualized by retrograde labeling with fluorogold. The presence of activated microglia was confirmed immunohistochemically using OX-42 monoclonal antibodies. Optic nerve axotomy produced RGC death and increased activation of microglia. No significant RGC loss was seen prior to 5 days and approximately 50% and 80-90% cell loss occurred at 7 and 14 days, respectively. Examination of the effects of tetracycline and minocycline on RGC survival at 7 days post-axotomy, revealed increased numbers of RGCs in minocycline-treated animals (75% of non-axotomized control) compared with vehicle-only (52% of control) and tetracycline-treated (58% of control) animals. The densities of RGCs (RGCs/mm2±S.D.) for control, vehicle-, tetracycline- and minocycline-treated axotomized animals were 1996±81, 1029±186, 1158±190 and 1497±312, respectively. The neuroprotective effect of minocycline seen at 7 days was transient, since RGCs present in minocycline-treated animals at 14 days post-axotomy (281±43, 14% of control) were not significantly different to vehicle-treated animals (225±47, 11% of control). OX-42 staining of activated retinal microglia was reduced in tetracycline- and minocycline-treated axotomized animals compared with axotomized animals receiving vehicle-only. These results demonstrate that systemic administration of the second-generation tetracycline derivative, minocycline, delays the death of axotomized RGCs by a mechanism that may be associated with inhibition of microglia activation. The neuroprotective efficacy of minocycline following optic nerve axotomy was superior to that of tetracycline.

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Effects of minocycline and tetracycline on retinal ganglion cell survival after axotomy

Resumen

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ASJC Scopus Subject Areas

PubMed: MeSH publication types

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