Transient ischemia of the retina results in massive degeneration of the retinotectal projection: long-term neuroprotection with brimonidine

Avilés‐Trigueros, Marcelino; Mayor–Torroglosa, S.; García–Avilés, A.; Lafuente, M.P.; Rodríguez, María Elena; Imperial, J Miralles de; Villegas‐Pérez, María Paz; Vidal‐Sanz, Manuel

doi:10.1016/s0014-4886(03)00298-x

Cited by 65 publications

(37 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…15 This damaged axonal transport can be prevented, almost fully, by BMD administered before induction of ischaemia. 15 Our group could also show that BMD protects against ischaemia-induced degeneration of the retinotectal projection 18 ( Figure 2), and preserves anterograde axonal transport as well as inner retinal layer function 19 ( Figure 3).…”

Section: Investigation Of Potential Neuroprotective Effects On Rgcsmentioning

confidence: 72%

Neuroprotection of retinal ganglion cell function and their central nervous system targets

Vidal‐Sanz

Villa

Avilés‐Trigueros

et al. 2007

Eye

View full text Add to dashboard Cite

Technological advances have enabled the observation of a large number of retinal ganglion cells (RGCs) in an objective manner. In animal models, it has been shown how retinal ischaemia induces profound functional and structural alterations of the inner retinal and RGC layers by 3 months. These findings reflect degeneration of the inner retinal layers, the RGC population and of the retinotectal projection. Functionally, this implies a permanent disconnection of the retina from its main retinorecipient target region in the brain. Brimonidine, a selective a-2 adrenergic agonist, has been shown to activate a-2 adrenergic receptors in the retina and promote the survival and function of RGCs post-injury. This agent may prevent or diminish ischaemia-induced alterations in the inner and RGC areas as well as in the main retinofugal projection. Understanding the pattern of degeneration that occurs in the major retinofugal pathway following retinal ischaemia will benefit ongoing studies conducted to develop neuroprotectant-based treatment strategies for progressive neuropathies such as glaucoma.

show abstract

Section: Investigation Of Potential Neuroprotective Effects On Rgcsmentioning

confidence: 72%

Neuroprotection of retinal ganglion cell function and their central nervous system targets

Vidal‐Sanz

Villa

Avilés‐Trigueros

et al. 2007

Eye

View full text Add to dashboard Cite

show abstract

“…RGC axons course through layer III of the SC to contact layer II neurons retinotopically (20). These can be visualized by intraocular injection of cholera toxin β-subunit (CTB), which labels the entire retinal projection via active uptake and transport (21,22). For a 5-mo C57 and a 5-mo DBA/2, CTB labeled the entire retinotopic projection in the SC except for the retinal optic disk, which does not contain RGCs ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…We used 2.5% isoflurane anesthesia for intravitreal injection of 1 μL (mice) or 2 μL (rats) of CTB conjugated to Alexa Fluor-488 or -594 (1 μL of 1% CTB in sterile PBS solution; Invitrogen) using a glass pipette (50-μm tip). CTB is an established marker for active uptake and transport and has been used successfully to assess the retinal projection to the SC in injury (21,22,45). Animals were transcardially perfused with 4% paraformaldehyde in PBS solution and tissues removed after 48 h of CTB activity, an established period for complete retinotopic mapping of the SC for mice and other small mammals (28).…”

Section: Methodsmentioning

confidence: 99%

Distal axonopathy with structural persistence in glaucomatous neurodegeneration

Crish

Sappington

Inman

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

313

482

View full text Add to dashboard Cite

An early hallmark of neuronal degeneration is distal transport loss and axon pathology. Glaucoma involves the degeneration of retinal ganglion cell (RGC) neurons and their axons in the optic nerve. Here we show that, like other neurodegenerations, distal axon injury appears early in mouse glaucoma. Where RGC axons terminate in the superior colliculus, reduction of active transport follows a retinotopic pattern resembling glaucomatous vision loss. Like glaucoma, susceptibility to transport deficits increases with age and is not necessarily associated with elevated ocular pressure. Transport deficits progress distal-to-proximal, appearing in the colliculus first followed by more proximal secondary targets and then the optic tract. Transport persists through the optic nerve head before finally failing in the retina. Although axon degeneration also progresses distal-to-proximal, myelinated RGC axons and their presynaptic terminals persist in the colliculus well after transport fails. Thus, distal transport loss is predegenerative and may represent a therapeutic target.axon transport | optic neuropathy | retinal ganglion cell | glaucoma | optic nerve

show abstract

“…Thus, it has been shown that a selective agonist of TrkB (BDNF receptor) causes a long term TrKB activation and significantly delays RGC degeneration after IOP increase and after optic nerve transection (Bai et al, 2010). Brimonidine, an α-2 adrenergic agonist, has been shown to neuroprotect RGCs after retinal ischemia (Lafuente et al, 2001Lafuente Lopez-Herrera et al, 2002;Vidal-Sanz et al, 2001a,b, 2007Aviles-Trigueros et al, 2003;Mayor-Torroglosa et al, 2005;Lonngren et al, 2006), after optic nerve crush (Wheeler et al, 1999) and after laser-induced ocular hypertension Lambert et al, 2011). A randomized trial comparing brimonidine and timolol (β-adrenergic antagonist) in low tension glaucomatous patients, has shown that the loss of visual field is statistically lower in brimonidine treatedpatients than in those treated with timolol, thus documenting, for the first time, its neuroprotective effect in human diseases (Krupin et al, 2011).…”

Section: Therapies To Increase the Resistance Of The Injured Neuronsmentioning

confidence: 99%

Anatomical and Molecular Responses Triggered in the Retina by Axonal Injury

Agudo‐Barriuso¹,

Nadal-Nicolás²,

Parrilla–Reverter³

et al. 2011

The Mystery of Glaucoma

Self Cite

View full text Add to dashboard Cite

Transient ischemia of the retina results in massive degeneration of the retinotectal projection: long-term neuroprotection with brimonidine

Cited by 65 publications

References 51 publications

Neuroprotection of retinal ganglion cell function and their central nervous system targets

Neuroprotection of retinal ganglion cell function and their central nervous system targets

Distal axonopathy with structural persistence in glaucomatous neurodegeneration

Anatomical and Molecular Responses Triggered in the Retina by Axonal Injury

Contact Info

Product

Resources

About