Success in Amblyopia Therapy as a Function of Age

Birnbaum, Martin H.; Koslowe, Kenneth; Sanet, Robert

doi:10.1097/00006324-197705000-00001

Cited by 68 publications

(31 citation statements)

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“…A number of clinical studies suggest that some recovery from amblyopia is possible well past the classically defined critical period in humans, which generally is considered to last up to ϳ9 years of age (Birnbaum et al, 1977;Simmers and Gray, 1999;Fronius et al, 2004). These studies indicate that long periods of depriving the dominant eye in amblyopes are needed for recovery of vision in the weak eye.…”

Section: Discussionmentioning

confidence: 99%

Visual Deprivation Modifies Both Presynaptic Glutamate Release and the Composition of Perisynaptic/Extrasynaptic NMDA Receptors in Adult Visual Cortex

Yashiro¹,

Corlew²,

Philpot

2005

J. Neurosci.

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Use-dependent modifications of synapses have been well described in the developing visual cortex, but the ability for experience to modify synapses in the adult visual cortex is poorly understood. We found that 10 d of late-onset visual deprivation modifies both presynaptic and postsynaptic elements at the layer 432/3 connection in the visual cortex of adult mice, and these changes differ from those observed in juveniles. Although visual deprivation in juvenile mice modifies the subunit composition and increases the current duration of synaptic NMDA receptors (NMDARs), no such effect is observed at synapses between layer 4 and layer 2/3 pyramidal neurons in adult mice. Surprisingly, visual deprivation in adult mice enhances the temporal summation of NMDAR-mediated currents induced by bursts of high-frequency stimulation. The enhanced temporal summation of NMDAR-mediated currents in deprived cortex could not be explained by a reduction in the rate of synaptic depression, because our data indicate that late-onset visual deprivation actually increases the rate of synaptic depression. Biochemical and electrophysiological evidence instead suggest that the enhanced temporal summation in adult mice could be accounted for by a change in the molecular composition of NMDARs at perisynaptic/extrasynaptic sites. Our data demonstrate that the experience-dependent modifications observed in the adult visual cortex are different from those observed during development. These differences may help to explain the unique consequences of sensory deprivation on plasticity in the developing versus mature cortex.

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Section: Discussionmentioning

confidence: 99%

Visual Deprivation Modifies Both Presynaptic Glutamate Release and the Composition of Perisynaptic/Extrasynaptic NMDA Receptors in Adult Visual Cortex

Yashiro¹,

Corlew²,

Philpot

2005

J. Neurosci.

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“…First, although binocular competition is thought to drive the loss of cortical connections mediating responses from the deprived eye, binocular competition cannot drive recovery because initially the deprived eye cannot activate cortical neurons. Second, clinical findings showing that recovery from amblyopia can occur after the critical period for the effects of monocular deprivation (Birnbaum et al, 1977) suggest that different sensitive periods characterize loss and recovery of visual acuity (Daw, 1998). In conclusion, it remains unclear whether the mechanisms that mediate loss of cortical binocular function can also contribute to recovery.…”

Section: Abstract: Creb; Ocular Dominance Plasticity; Recovery Of Fumentioning

confidence: 99%

Different Mechanisms for Loss and Recovery of Binocularity in the Visual Cortex

et al. 2002

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Diverse molecular mechanisms have been discovered that mediate the loss of responses to the deprived eye during monocular deprivation. cAMP/Ca 2ϩ response element-binding protein (CREB) function, in particular, is thought to be essential for ocular dominance plasticity during monocular deprivation. In contrast, we have very little information concerning the molecular mechanisms of recovery from the effects of monocular deprivation, even though this information is highly relevant for understanding cortical plasticity. To test the involvement of CREB activation in recovery of responses to the deprived eye, we used herpes simplex virus (HSV) to express in the primary visual cortex a dominant-negative form of CREB (HSV-mCREB) containing a single point mutation that prevents its activation. This mutant was used to suppress CREB function intracortically during the period when normal vision was restored in two protocols for recovery from monocular deprivation: reverse deprivation and binocular vision. In the reverse deprivation model, inhibition of CREB function prevented loss of responses to the newly deprived eye but did not prevent simultaneous recovery of responses to the previously deprived eye. Full recovery of cortical binocularity after restoration of binocular vision was similarly unaffected by HSV-mCREB treatment. The HSV-mCREB injections produced strong suppression of CREB function in the visual cortex, as ascertained by both DNA binding assays and immunoblot analysis showing a decrease in the expression of the transcription factor C/EBP␤, which is regulated by CREB. These results show a mechanistic dichotomy between loss and recovery of neural function in visual cortex; CREB function is essential for loss but not for recovery of deprived eye responses.

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“…Since Kupfer's study, there have been many reports of improvement in acuity of older people with amblyopia (e.g. Birnbaum et al 1977;Wick et al 1992). A case report showed that occlusion therapy appeared to improve not only visual acuity, but also position acuity in an adult strabismic amblyope.…”

Section: Introductionmentioning

confidence: 99%

Improving the performance of the amblyopic visual system

Levi

2008

Phil. Trans. R. Soc. B

129

116

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Experience-dependent plasticity is closely linked with the development of sensory function; however, there is also growing evidence for plasticity in the adult visual system. This review re-examines the notion of a sensitive period for the treatment of amblyopia in the light of recent experimental and clinical evidence for neural plasticity. One recently proposed method for improving the effectiveness and efficiency of treatment that has received considerable attention is 'perceptual learning'. Specifically, both children and adults with amblyopia can improve their perceptual performance through extensive practice on a challenging visual task. The results suggest that perceptual learning may be effective in improving a range of visual performance and, importantly, the improvements may transfer to visual acuity. Recent studies have sought to explore the limits and time course of perceptual learning as an adjunct to occlusion and to investigate the neural mechanisms underlying the visual improvement. These findings, along with the results of new clinical trials, suggest that it might be time to reconsider our notions about neural plasticity in amblyopia.

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Success in Amblyopia Therapy as a Function of Age

Cited by 68 publications

References 0 publications

Visual Deprivation Modifies Both Presynaptic Glutamate Release and the Composition of Perisynaptic/Extrasynaptic NMDA Receptors in Adult Visual Cortex

Visual Deprivation Modifies Both Presynaptic Glutamate Release and the Composition of Perisynaptic/Extrasynaptic NMDA Receptors in Adult Visual Cortex

Different Mechanisms for Loss and Recovery of Binocularity in the Visual Cortex

Improving the performance of the amblyopic visual system

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