Comparative analysis of structural modifications induced by monocular retinal inactivation and monocular deprivation in the developing cat lateral geniculate nucleus

Duffy, Kevin R.; Crowder, Nathan A.; Heynen, Arnold J.; Bear, Mark F.

doi:10.1002/cne.25493

Cited by 5 publications

(5 citation statements)

References 66 publications

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“…Animals subjected to monocular inactivation after MD showed a much larger plasticity reduction, with prior MD reducing the loss of neurofilament by about 90%. This was surprising because monocular inactivation can produce much larger anatomical effects in the dLGN compared to MD ( Kuppermann and Kasamatsu 1983 ; Duffy et al, 2023 ). The near complete lack of neurofilament loss with monocular inactivation after a period of MD may derive from the longer duration of prior MD (6 weeks) that was imposed before inactivation was initiated.…”

Section: Discussionmentioning

confidence: 99%

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Early monocular deprivation reduces the capacity for neural plasticity in the cat visual system

Henneberry,

Elgallad,

Smith

et al. 2023

Cerebral Cortex Communications

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Obstruction of vision to one eye during early postnatal development elicits neural modifications in the visual system that last a lifetime. Research in rodents has revealed that an early and transient monocular deprivation (MD) can produce an enduring alteration to the framework of neural connections within visual cortex. This lasting trace of early MD enables an enhanced effect of a second MD imposed on the same eye in adulthood. In the current study, we examined whether the modification of plasticity potential was bidirectional by assessing whether the effect of early and brief MD attenuated the impact of a subsequent MD when applied to the fellow eye. Results were clear in showing that animals with an early MD exhibited a smaller response to later visual deprivation of the fellow eye. Compared to controls, animals with a history of MD exhibited less atrophy of neurons, and a smaller loss of neurofilament labeling within the dorsal lateral geniculate nucleus. The shift in cortical ocular dominance elicited by MD was also smaller in animals with a prior MD. These results indicate that early MD elicits abiding and eye-specific neural modifications that can selectively alter plasticity potential in the visual system.

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Section: Discussionmentioning

confidence: 99%

“…2012 ; Duffy et al. 2018 ; Duffy et al. 2023 ), and their tissues were reanalyzed alongside those reared specifically for the current study.…”

Section: Methodsmentioning

confidence: 99%

Early monocular deprivation reduces the capacity for neural plasticity in the cat visual system

Henneberry,

Elgallad,

Smith

et al. 2023

Cerebral Cortex Communications

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“…To be considered as a treatment for human MD, it will be of paramount importance to demonstrate full recovery of the inactivated eye in a primate model. Assessments to date in cats and monkeys have revealed no ocular pathology after inactivation for up to 10 days ( Foeller and Tychsen, 2019 ; DiCostanzo et al, 2020 ; Duffy et al, 2023 ; Hogan et al, 2023 ). Figure 4 demonstrates restoration of VEPs following brief monocular inactivation in a cat (A) and macaque monkey (B).…”

Section: Therapeutic Innovationsmentioning

confidence: 99%

“… Data from cat and monkey revealing that the effect of intravitreal injection of TTX is reversible. VEPs (solid circles) measured from V1 in a cat ( A ; Duffy et al, 2023 ) and monkey ( B ; preliminary data) using scalp electrodes show a reduction to non-visual baseline levels (open circles) after TTX injection. Measurement of VEPs post-inactivation reveal a full recovery back to pre-inactivation levels for both species, indicating that the effect of inactivation on VEPs is temporary.…”

Section: Therapeutic Innovationsmentioning

confidence: 99%

Human deprivation amblyopia: treatment insights from animal models

Duffy,

Bear,

Patel

et al. 2023

Front. Neurosci.

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Amblyopia is a common visual impairment that develops during the early years of postnatal life. It emerges as a sequela to eye misalignment, an imbalanced refractive state, or obstruction to form vision. All of these conditions prevent normal vision and derail the typical development of neural connections within the visual system. Among the subtypes of amblyopia, the most debilitating and recalcitrant to treatment is deprivation amblyopia. Nevertheless, human studies focused on advancing the standard of care for amblyopia have largely avoided recruitment of patients with this rare but severe impairment subtype. In this review, we delineate characteristics of deprivation amblyopia and underscore the critical need for new and more effective therapy. Animal models offer a unique opportunity to address this unmet need by enabling the development of unconventional and potent amblyopia therapies that cannot be pioneered in humans. Insights derived from studies using animal models are discussed as potential therapeutic innovations for the remediation of deprivation amblyopia. Retinal inactivation is highlighted as an emerging therapy that exhibits efficacy against the effects of monocular deprivation at ages when conventional therapy is ineffective, and recovery occurs without apparent detriment to the treated eye.

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“…Unlike monocular lid closure that deprives form vision in the affected eye, MI eliminates impulses from retinal ganglion cells. That MI can exhibit greater efficacy to elicit neural changes in the dLGN compared to lid closure (Duffy et al, 2018(Duffy et al, , 2023, raises the possibility that ocular refractive error and axial length may be altered by MI. If MI modifies either of these characteristics, it could produce imbalanced focusing ability between the eyes in patients treated for amblyopia.…”

Section: Introductionmentioning

confidence: 99%

Investigation of the efficacy and safety of retinal inactivation as a treatment for amblyopia in cats

et al. 2023

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IntroductionDeprivation of normal vision early in postnatal development elicits modifications of neural circuitry within the primary visual pathway that can cause a severe and intractable vision impairment (amblyopia). In cats, amblyopia is often modeled with monocular deprivation (MD), a procedure that involves temporarily closing the lids of one eye. Following long-term MD, brief inactivation of the dominant eye’s retina can promote recovery from the anatomical and physiological effects of MD. In consideration of retinal inactivation as a viable treatment for amblyopia it is imperative to compare its efficacy against conventional therapy, as well as assess the safety of its administration.MethodsIn the current study we compared the respective efficacies of retinal inactivation and occlusion of the dominant eye (reverse occlusion) to elicit physiological recovery from a prior long-term MD in cats. Because deprivation of form vision has been associated with development of myopia, we also examined whether ocular axial length or refractive error were altered by a period of retinal inactivation.ResultsThe results of this study demonstrate that after a period of MD, inactivation of the dominant eye for up to 10 days elicited significant recovery of visually-evoked potentials that was superior to the recovery measured after a comparable duration of reverse occlusion. After monocular retinal inactivation, measurements of ocular axial length and refractive error were not significantly altered from their pre-inactivation values. The rate of body weight gain also was not changed during the period of inactivation, indicating that general well-being was not affected.DiscussionThese results provide evidence that inactivation of the dominant eye after a period of amblyogenic rearing promotes better recovery than eye occlusion, and this recovery was achieved without development of form-deprivation myopia.

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Comparative analysis of structural modifications induced by monocular retinal inactivation and monocular deprivation in the developing cat lateral geniculate nucleus

Cited by 5 publications

References 66 publications

Early monocular deprivation reduces the capacity for neural plasticity in the cat visual system

Early monocular deprivation reduces the capacity for neural plasticity in the cat visual system

Human deprivation amblyopia: treatment insights from animal models

Investigation of the efficacy and safety of retinal inactivation as a treatment for amblyopia in cats

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