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Retinal Electrophysiology Is a Viable Preclinical Biomarker for Drug Penetrance into the Central Nervous System.

Charng J, He Z, Vingrys AJ, Fish RL, Gurrell R, Bui BV, Nguyen CT - J Ophthalmol (2016)

Bottom Line: In conscious animals, systemic administration of muscimol resulted in retinal and brain biopotential changes, whereas systemic delivery of isoguvacine did not.General anaesthesia confounded these outcomes.Conclusions.

View Article: PubMed Central - PubMed

Affiliation: Department of Optometry & Vision Sciences, University of Melbourne, Parkville, VIC 3010, Australia.

ABSTRACT
Objective. To examine whether retinal electrophysiology is a useful surrogate marker of drug penetrance into the central nervous system (CNS). Materials and Methods. Brain and retinal electrophysiology were assessed with full-field visually evoked potentials and electroretinograms in conscious and anaesthetised rats following systemic or local administrations of centrally penetrant (muscimol) or nonpenetrant (isoguvacine) compounds. Results. Local injections into the eye/brain bypassed the blood neural barriers and produced changes in retinal/brain responses for both drugs. In conscious animals, systemic administration of muscimol resulted in retinal and brain biopotential changes, whereas systemic delivery of isoguvacine did not. General anaesthesia confounded these outcomes. Conclusions. Retinal electrophysiology, when recorded in conscious animals, shows promise as a viable biomarker of drug penetration into the CNS. In contrast, when conducted under anaesthetised conditions confounds can be induced in both cortical and retinal electrophysiological recordings.

No MeSH data available.


Related in: MedlinePlus

Cortical electrophysiology following conscious isoguvacine/muscimol injections. VEP responses in animals ((a)–(d), n = 7 for each drug group) at conscious baseline (black lines, average of vehicle injections in conscious groups) compared to (a) intramuscular and (b) intravitreal injection of isoguvacine (red) and (c) intramuscular and (d) intravitreal injection of muscimol (blue). (e)–(h) summarise VEP parameters (average ± SEM) following isoguvacine or muscimol injections via different routes (see method for details). Grey areas indicate 95% CI of the particular VEP parameter in all conscious baseline recordings. P1, P2, and N1 are marked in (a), with P2 taken as the first positive inflection following N1. ∗p < 0.05.
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fig3: Cortical electrophysiology following conscious isoguvacine/muscimol injections. VEP responses in animals ((a)–(d), n = 7 for each drug group) at conscious baseline (black lines, average of vehicle injections in conscious groups) compared to (a) intramuscular and (b) intravitreal injection of isoguvacine (red) and (c) intramuscular and (d) intravitreal injection of muscimol (blue). (e)–(h) summarise VEP parameters (average ± SEM) following isoguvacine or muscimol injections via different routes (see method for details). Grey areas indicate 95% CI of the particular VEP parameter in all conscious baseline recordings. P1, P2, and N1 are marked in (a), with P2 taken as the first positive inflection following N1. ∗p < 0.05.

Mentions: Intramuscular injection of isoguvacine in conscious rats had little effect on the VEP waveform (Figure 3(a)) or its parameters as shown in Figures 3(e)–3(h) (p = 0.14 to 0.74). Direct ICV injection of isoguvacine (Figure 3(b)) significantly delayed the P2 component of the VEP (Figure 3(h), 17 ± 1%, p < 0.05). P2-N1 amplitude was not significantly affected (Figure 3(f), −20 ± 19%, p = 0.21).


Retinal Electrophysiology Is a Viable Preclinical Biomarker for Drug Penetrance into the Central Nervous System.

Charng J, He Z, Vingrys AJ, Fish RL, Gurrell R, Bui BV, Nguyen CT - J Ophthalmol (2016)

Cortical electrophysiology following conscious isoguvacine/muscimol injections. VEP responses in animals ((a)–(d), n = 7 for each drug group) at conscious baseline (black lines, average of vehicle injections in conscious groups) compared to (a) intramuscular and (b) intravitreal injection of isoguvacine (red) and (c) intramuscular and (d) intravitreal injection of muscimol (blue). (e)–(h) summarise VEP parameters (average ± SEM) following isoguvacine or muscimol injections via different routes (see method for details). Grey areas indicate 95% CI of the particular VEP parameter in all conscious baseline recordings. P1, P2, and N1 are marked in (a), with P2 taken as the first positive inflection following N1. ∗p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4863103&req=5

fig3: Cortical electrophysiology following conscious isoguvacine/muscimol injections. VEP responses in animals ((a)–(d), n = 7 for each drug group) at conscious baseline (black lines, average of vehicle injections in conscious groups) compared to (a) intramuscular and (b) intravitreal injection of isoguvacine (red) and (c) intramuscular and (d) intravitreal injection of muscimol (blue). (e)–(h) summarise VEP parameters (average ± SEM) following isoguvacine or muscimol injections via different routes (see method for details). Grey areas indicate 95% CI of the particular VEP parameter in all conscious baseline recordings. P1, P2, and N1 are marked in (a), with P2 taken as the first positive inflection following N1. ∗p < 0.05.
Mentions: Intramuscular injection of isoguvacine in conscious rats had little effect on the VEP waveform (Figure 3(a)) or its parameters as shown in Figures 3(e)–3(h) (p = 0.14 to 0.74). Direct ICV injection of isoguvacine (Figure 3(b)) significantly delayed the P2 component of the VEP (Figure 3(h), 17 ± 1%, p < 0.05). P2-N1 amplitude was not significantly affected (Figure 3(f), −20 ± 19%, p = 0.21).

Bottom Line: In conscious animals, systemic administration of muscimol resulted in retinal and brain biopotential changes, whereas systemic delivery of isoguvacine did not.General anaesthesia confounded these outcomes.Conclusions.

View Article: PubMed Central - PubMed

Affiliation: Department of Optometry & Vision Sciences, University of Melbourne, Parkville, VIC 3010, Australia.

ABSTRACT
Objective. To examine whether retinal electrophysiology is a useful surrogate marker of drug penetrance into the central nervous system (CNS). Materials and Methods. Brain and retinal electrophysiology were assessed with full-field visually evoked potentials and electroretinograms in conscious and anaesthetised rats following systemic or local administrations of centrally penetrant (muscimol) or nonpenetrant (isoguvacine) compounds. Results. Local injections into the eye/brain bypassed the blood neural barriers and produced changes in retinal/brain responses for both drugs. In conscious animals, systemic administration of muscimol resulted in retinal and brain biopotential changes, whereas systemic delivery of isoguvacine did not. General anaesthesia confounded these outcomes. Conclusions. Retinal electrophysiology, when recorded in conscious animals, shows promise as a viable biomarker of drug penetration into the CNS. In contrast, when conducted under anaesthetised conditions confounds can be induced in both cortical and retinal electrophysiological recordings.

No MeSH data available.


Related in: MedlinePlus