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Inhibition of form-deprivation myopia by a GABAAOr receptor antagonist, (1,2,5,6-tetrahydropyridin-4-yl) methylphosphinic acid (TPMPA), in guinea pigs

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Abstract

Purpose

To investigate the effects of the relatively selective GABAAOr receptor antagonist (1,2,5,6-tetrahydropyridin-4-yl) methylphosphinic acid (TPMPA) on form-deprivation myopia (FDM) in guinea pigs.

Methods

A diffuser was applied monocularly to 30 guinea pigs from day 10 to 21. The animals were randomized to one of five treatment groups. The deprived eye received daily sub-conjunctival injections of 100 μl TPMPA at a concentration of (i) 0.03 %, ( ii) 0.3 %, or (iii) 1 %, a fourth group (iv) received saline injections, and another (v) no injections. The fellow eye was left untreated. An additional group received no treatment to either eye. Prior to and at the end of the treatment period, refraction and ocular biometry were performed.

Results

Visual deprivation produced relative myopia in all groups (treated versus untreated eyes, P < 0.05). The amount of myopia was significantly affected by the drug treatment (one-way ANOVA, P < 0.0001); myopia was less in deprived eyes receiving either 0.3 % or 1 % TPMPA (saline = −4.38 ± 0.57D, 0.3 % TPMPA = −3.00 ± 0.48D, P < 0.01; 1 % TPMPA = −0.88 ± 0.51D, P < 0.001). The degree of axial elongation was correspondingly less (saline = 0.13 ± 0.02 mm, 0.3 % TPMPA = 0.09 ± 0.01 mm, P < 0.01, 1 % TPMPA = 0.02 ± 0.01 mm, P < 0.001) as was the VC elongation (saline = 0.08 ± 0.01 mm, 0.3 % TPMPA = 0.05 ± 0.01 mm, P < 0.01, 1 % TPMPA = 0.01 ± 0.01 mm; P < 0.001). ACD and LT were not affected (one-way ANOVA, P > 0.05). One percent TPMPA was more effective at inhibiting myopia than 0.3 % (P < 0.01), and 0.03 % did not appreciably inhibit the myopia (0.03 % TPMPA versus saline, P > 0.05).

Conclusions

Sub-conjunctival injections of TPMPA inhibit FDM in guinea pig models in a dose-dependent manner.

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Abbreviations

TPMPA:

(1,2,5,6-tetrahydropyridin-4-yl) methylphosphinic acid

FDM:

Form-deprivation myopia

SER:

Spherical equivalent refraction

AL:

Axial length

VCD:

Vitreous chamber depth

ACD:

Anterior chamber depth

LT:

Lens thickness

RPE:

Retinal pigment epithelium.

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Acknowledgments

This work was supported by a grant from the National Natural Science Foundation of China (No. 81271038), and a grant from the Department of Science and Technology of Shandong Province of China (No. ZR2012HM022) to ZYC.

Conflicts of interest

The authors have no conflict of interests to declare.

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Jinan, Shandong, 250012, China

    Zhen-Ying Cheng

  2. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, Shandong, China

    Xu-Ping Wang

  3. School of Optometry and Vision Science, Faculty of Health, and Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia

    Katrina L. Schmid

  4. Department of Ophthalmology, The Second People’s Hospital of Jinan, Jinan, Shandong, China

    Xu-Guang Han

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  1. Zhen-Ying Cheng
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Correspondence to Zhen-Ying Cheng.

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Cheng, ZY., Wang, XP., Schmid, K.L. et al. Inhibition of form-deprivation myopia by a GABAAOr receptor antagonist, (1,2,5,6-tetrahydropyridin-4-yl) methylphosphinic acid (TPMPA), in guinea pigs. Graefes Arch Clin Exp Ophthalmol 252, 1939–1946 (2014). https://doi.org/10.1007/s00417-014-2765-5

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  • DOI: https://doi.org/10.1007/s00417-014-2765-5

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