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Maturation of Rb+ and PAH accumulation by rabbit anterior uvea and choroid plexus
Insights
Newborn rabbit eyes show developing para-aminohippuric acid (PAH) and rubidium (86Rb+) transport in the anterior uvea, reaching adult levels later in development. The choroid plexus demonstrates mature transport from birth.
Area of Science:
- Ocular Physiology
- Developmental Biology
- Pharmacokinetics
Background:
- The anterior uvea, ciliary processes, and choroid plexus are critical ocular tissues involved in fluid homeostasis and drug transport.
- Understanding the developmental trajectory of active transport mechanisms in these tissues is essential for predicting ocular drug disposition and efficacy in neonates.
Purpose of the Study:
- To investigate the ontogeny of para-aminohippuric acid (PAH) and rubidium (86Rb+) accumulation in rabbit ocular tissues.
- To assess the impact of early-life penicillin exposure on these transport processes.
Main Methods:
- In vitro accumulation assays using radioactive 3H-PAH and 86Rb+ in ocular tissues (anterior uvea, ciliary processes, choroid plexus) from rabbits of various ages (1 day to 90 days).
- Measurement of tissue-to-media ratios (T/M) to quantify substrate accumulation.
- Evaluation of the effect of daily penicillin injections on PAH accumulation in the anterior uvea.
Main Results:
- Anterior uvea PAH accumulation was low at birth, increasing to adult levels by 21 days of age.
- Anterior uvea 86Rb+ accumulation (Na+, K+-ATPase activity) was elevated at birth and remained high through 28 days, returning to adult levels by 60 days.
- Choroid plexus accumulation of both 3H-PAH and 86Rb+ was similar to adult levels from 1 day of age and did not change significantly over 90 days.
- Penicillin treatment did not affect anterior uvea PAH accumulation.
Conclusions:
- The anterior uvea exhibits a postnatal maturation of PAH and rubidium transport systems.
- The choroid plexus demonstrates mature transport function early in postnatal life.
- Early penicillin exposure does not appear to significantly alter PAH transport in the developing anterior uvea.
Abstract:
In vitro accumulation of radioactive para-aminohippuric acid (3H-PAH) and rubidium (86Rb+) by the anterior uvea, ciliary processes, and the choroid plexus was evaluated in tissues from newborn and various aged rabbits. Accumulation of PAH was present in the anterior uvea at 1 day of age (tissue to media ratio, T/M, of 2.1 +/- 0.2) and remained at this level for the first 14 days of life. Accumulation did not rise to adult levels until 21 days of age (T/M 5.5 +/- 0.6). Rubidium accumulation in the anterior uvea, a measure of Na+, K+-pump activity, was higher than adult values 6 hr after birth (T/M25.2 +/- 0.9). Activity remained elevated through day 28 and did not fall to adult levels until day 60 (T/M 13.4 +/- 0.6). Accumulation studies on isolated ciliary processes were similar to those obtained from anterior uveal tissue. Daily subcutaneous injections of penicillin (300,000 units/kg/day) for 1 week had no effect on anterior uvea PAH accumulation (penicillin T/M was 1.7 +/- 0.1 and saline control T/M was 2.0 +/- 0.2). Accumulation of either 3H-PAH or 86Rb+ by the choroid plexus was present 1 day after birth in amounts that were similar to adult values and did not change during the 90 days of testing.