Claxton A. Baer

Stages of improvement in visual fields after pituitary tumor resection

PURPOSE To use static threshold perimetry to examine the stages of improvement and the potential for late improvement of visual fields after surgical resection of pituitary adenomas causing visual loss from compression of the anterior visual pathways. METHODS Retrospective review of charts of patients with pituitary tumors and abnormal static threshold perimetry before or soon after treatment who had subsequent visual fields. Quantification of the visual field mean deviation overall, superotemporally, and inferotemporally was performed and compared between visits. Postoperative visits were considered in five time periods: visit 1 (surgery to 1 week), visit 2 (1 month to 4 months), visit 3 (6 months to 1 year), visit 4 (2 years), and visit 5 (3 or more years). RESULTS Sixty-two patients were included (33 men and 29 women; mean age 54 years [SD +/- 15 years; range, 22 to 83 years]). At visit 1, the relative improvement of the overall mean deviation for the right eye was 30.8% (P =.01) and for the left eye was 13.7% (P =.3067). At visit 2, the relative improvement of the overall mean deviation for the right eye was 30. 4% (P =.0142) and for the left eye was 32.6% (P =.0092). At visits 1 and 2, the inferotemporal quadrants were the quadrants with greatest improvement (visit 1, right eye, 37.8% [P =.0082]; visit 2, left eye, 30.8% [P =.0074]). At visits 3, 4, and 5, an overall trend toward mild improvement was observed with statistical significance only for the inferotemporal quadrant of the left eye from visit 2 to visit 3, which improved 19.7% (P =.0270). CONCLUSION The pattern of recovery of visual function after decompression of the anterior visual pathways suggests at least three phases of improvement. The early fast phase (surgery to 1 week) of improvement may lead to normalization of visual fields in some individuals. The early slow phase (1 month to 4 months) is the period of most notable improvement. A late phase (6 months to 3 years) of mild improvement does not appear significant overall but may be marked in some individuals. Each of these phases may have one or more mechanisms underlying the observed improvement.

INTERPHOTORECEPTOR RETINOID-BINDING PROTEIN (IRBP) : EXPRESSION IN THE ADULT AND DEVELOPING XENOPUS RETINA

Apposition of the neural retina and pigment epithelium is critical to photoreceptor development and function. Interphotoreceptor retinoid‐binding protein (IRBP) is a major component of the extracellular matrix separating these epithelia in the African clawed frog Xenopus laevis (Gonzalez‐Fernandez et al., [1993], J. Cell Sci. 105:7–21). In the adult retina, IRBP appears to mediate the transport of hydrophobic molecules, particularly retinoids and fatty acids, within the hydrophilic extracellular domain. In this paper, we compare the distribution of IRBP and its mRNA in adult and embryonic Xenopus retina. Xenopus IRBP antisense RNA, labeled with tritium or digoxigenin, was used for in situ hybridization studies. For immunohistochemistry, we used an antiserum against Xenopus IRBP expressed in Escherichia coli. In the adult, we found that IRBP is synthesized at similar levels by both rods and cones. The protein is restricted to the interphotoreceptor matrix, with lesser amounts in the pigment epithelial cytoplasm. In the embryo, expression of the mRNA for IRBP is restricted to the central retina, where photoreceptor differentiation has taken place. By contrast, the protein is distributed throughout the embryonic subretinal space. Therefore, the presence of IRBP precedes photoreceptor differentiation. In summary, IRBP is synthesized by both rods and cones and may be internalized by the pigment epithelium. In the embryo, IRBP is synthesized by the central retina and diffuses through the matrix, reaching the undifferentiated peripheral retina. In view of its ligand‐binding properties, diffusion of IRBP may provide the peripheral neural retina with a vehicle to transport retinoids and docosahexaenoic acid (molecules critical to normal retinal development) from the pigment epithelium.

Expression and characterization of the fourth repeat of Xenopus interphotoreceptor retinoid-binding protein in E. coli

Interphotoreceptor retinoid-binding protein (IRBP) is an extracellular glycolipoprotein which in higher vertebrates has a 4-repeat structure and carries endogenous vitamin A and fatty acids. The location of IRBPs 1-2 binding sites for retinol is unknown. To begin to understand which repeat(s) are responsible for ligand-binding, we expressed the fourth repeat of Xenopus IRBP in E. coli to determine if it could by itself bind all-trans retinol. Our expression studies used a polyhistidine fusion domain to purify the recombinant protein directly from inclusion bodies. The fusion protein could be renatured without aggregation if refolded at a sufficiently dilute concentration (< 3 microM). The recombinant fourth repeat of Xenopus IRBP binds [3H]all-trans retinol and the fluorescence of this ligand increases 8-fold upon binding. The binding is saturable with a Kd = 0.4 microM. The expression of recombinant IRBP fragments as fusion proteins in prokaryotes will be useful for defining the structural requirements for ligand binding by this interesting protein.