TY - JOUR
T1 - Consequences of puberty on efficacy of intraocular pressure-lowering drugs in male Dutch-belted rabbits
AU - Hays, Cassandra L.
AU - Okafor, Kingsley C.
AU - Fan, Shan
AU - High, Robin
AU - Singh, Dhirendra P.
AU - Toris, Carol B.
N1 - Funding Information:
Supported by Research to Prevent Blindness (University of Nebraska Medical Center and Case Western Reserve University).
Publisher Copyright:
© Copyright 2018, Mary Ann Liebert, Inc.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Purpose: To investigate the changes in intraocular pressure (IOP), aqueous flow, and outflow facility, as well as efficacy of IOP-lowering drugs before and after sexual development in rabbits. Methods: Male Dutch-belted rabbits were studied at night between the ages of 8 and 44 weeks. During these times, body weight, testicular volume, and serum testosterone were measured to monitor sexual maturity. Ocular measurements included anterior chamber depth, central corneal thickness, IOP, aqueous flow, and outflow facility. Systemic acetazolamide or topical timolol, latanoprost, or saline were administered pre- and postpuberty to assess drug effects on these parameters. Results: Body weight, testicular volume, and serum testosterone increased until 28 weeks of age. IOP increased during prepuberty (R 2 = 0.49, P = 0.003), dropped significantly during puberty, rising again immediate postpuberty, and changing little thereafter. Postpuberty compared with prepuberty found higher IOP (P < 0.0001), slower aqueous flow (P = 0.008), lower outflow facility (not statistically significant, P = 0.07), increased central cornea thickness, and increased anterior chamber volume. Timolol lowered IOP both pre- and postpuberty, whereas, latanoprost and acetazolamide decreased IOP postpuberty only. Conclusions: As male rabbits mature, the cornea thickens and the anterior chamber volume increases. At the same time, aqueous flow slows, yet, IOP increases. This suggests that decreased outflow facility and/or increased episcleral venous pressure might contribute to the puberty-related changes in IOP. Underdevelopment of tissues of the outflow pathways may contribute to the differences in drug efficacy in rabbits when young compared with after sexual maturity.
AB - Purpose: To investigate the changes in intraocular pressure (IOP), aqueous flow, and outflow facility, as well as efficacy of IOP-lowering drugs before and after sexual development in rabbits. Methods: Male Dutch-belted rabbits were studied at night between the ages of 8 and 44 weeks. During these times, body weight, testicular volume, and serum testosterone were measured to monitor sexual maturity. Ocular measurements included anterior chamber depth, central corneal thickness, IOP, aqueous flow, and outflow facility. Systemic acetazolamide or topical timolol, latanoprost, or saline were administered pre- and postpuberty to assess drug effects on these parameters. Results: Body weight, testicular volume, and serum testosterone increased until 28 weeks of age. IOP increased during prepuberty (R 2 = 0.49, P = 0.003), dropped significantly during puberty, rising again immediate postpuberty, and changing little thereafter. Postpuberty compared with prepuberty found higher IOP (P < 0.0001), slower aqueous flow (P = 0.008), lower outflow facility (not statistically significant, P = 0.07), increased central cornea thickness, and increased anterior chamber volume. Timolol lowered IOP both pre- and postpuberty, whereas, latanoprost and acetazolamide decreased IOP postpuberty only. Conclusions: As male rabbits mature, the cornea thickens and the anterior chamber volume increases. At the same time, aqueous flow slows, yet, IOP increases. This suggests that decreased outflow facility and/or increased episcleral venous pressure might contribute to the puberty-related changes in IOP. Underdevelopment of tissues of the outflow pathways may contribute to the differences in drug efficacy in rabbits when young compared with after sexual maturity.
KW - aqueous flow
KW - intraocular pressure
KW - puberty
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U2 - 10.1089/jop.2016.0168
DO - 10.1089/jop.2016.0168
M3 - Article
C2 - 28820646
AN - SCOPUS:85042193725
VL - 34
SP - 76
EP - 84
JO - Journal of Ocular Pharmacology
JF - Journal of Ocular Pharmacology
SN - 1080-7683
IS - 1-2
ER -