Biomedical subjects

John R Hetling

Publications and source records attributed to John R Hetling.

4 recordsLinked to original sources

PubMed2005

Features of visual function in the naked mole-rat Heterocephalus glaber.

The eyes and visual capacity of the naked mole-rat, Heterocephalus glaber, a subterranean rodent, were evaluated using anatomical, biochemical, and functional assays, and compared to other rodents of similar body size (mouse and gerbil). The eye is small compared to mouse, yet possesses cornea, lens, and retina with typical mammalian organization. The optic nerve cross-sectional area and fiber density are approximately 10% and approximately 50% that of gerbil, respectively. Levels per unit retinal area of 11-cis and all-trans retinal, derivatives of vitamin A associated with the visual cycle, are comparable to mouse. The corneal electroretinogram (ERG) exhibits early and late negative components that scale with flash strength; raising the body temperature of this poikilothermic animal from 30 degrees C (normal for H. glaber ) to 37 degrees C (normal for mouse) revealed an ERG response with typically mammalian features, but greatly attenuated and with slower kinetics. Leaving the nest chamber was a behavior correlated with light onset displayed preferentially by breeding females. Optical models of five mole-rat eyes suggest reasonable, but variable, image formation at the retina, possibly related to age. Results are consistent with amorphous light detection, possibly useful for circadian entrainment or escape behavior in the event of tunnel breeches.

Adaptation, Ocular↗

PubMed2004

Dark adaptation of rod photoreceptors in normal subjects, and in patients with Stargardt disease and an ABCA4 mutation.

PURPOSE: Psychophysical and electroretinographic (ERG) studies indicate that patients with Stargardt disease exhibit abnormally slow rod dark adaptation after illumination that bleaches a substantial fraction of rhodopsin. However, relatively little information is available concerning rod recovery in this disease after weaker adapting (i.e., conditioning) light. With the use of a paired-flash ERG method, properties of the derived rod response to a low-bleach (<1%) but rod-saturating conditioning flash were investigated in seven normal subjects and in five Stargardt patients with identified sequence variations in the ABCA4 gene. METHODS: In the first of two experiments, the interval between a fixed conditioning flash (67 or 670 scotopic cd s m(-2)) and a bright probe flash of fixed strength was varied to determine the falling-phase kinetics of the derived rod response to the conditioning flash. In the second, the instantaneous amplitude-intensity function for the rod response at an intermediate stage of recovery from the conditioning flash was determined by presenting a test flash of various strengths at a fixed time after the conditioning flash, and a probe flash at 200 ms after the test flash. RESULTS: The maximum peak amplitude of the dark-adapted, rod-mediated a-wave determined in Stargardt patients (211 +/- 87 microV) was on average lower than that determined in normal subjects (325 +/- 91 microV; P = 0.06). The derived rod response to the 670 scotopic cd s m(-2) conditioning flash determined in normal subjects and Stargardt patients exhibited a biphasic recovery, and the kinetics of the early stage of this recovery were similar in the two subject groups. For both normal subjects and patients, normalized amplitude-intensity functions describing the dark-adapted derived rod response exhibited half-saturation at approximately 1.5 log scotopic troland second. In both groups, the normalized amplitude-intensity function determined at approximately 2 seconds after the 67 scotopic cd s m(-2) conditioning flash and at approximately 9 seconds after the 670 scotopic cd s m(-2) conditioning flash exhibited an average desensitization (i.e., an increase of test flash strength at half-saturation) of approximately 0.5 to 0.6 log unit relative to that determined under dark-adapted conditions. CONCLUSIONS: The results indicate that, despite a reduction in the average dark-adapted maximum a-wave amplitude in the Stargardt/ABCA4 patients, the early-stage recovery kinetics of the derived rod response to a low-bleaching conditioning flash as well as the lingering rod desensitization produced by such a flash are similar to those determined in normal subjects.

ATP-Binding Cassette Transporters↗

PubMed2004

Neural prostheses for vision: designing a functional interface with retinal neurons.

A number of prevalent eye diseases exist which may lead to partial or total blindness, and for which there are currently no cures or means by which to restore lost sight. Based on recent progress, it has become apparent that artificial prosthetic devices, which would use electrical stimulation of neurons in the visual pathway to elicit visual percepts, are likely to some day become a viable treatment for patients blinded by these diseases. A number of recent scientific reviews have summarized general functional electrical stimulation (FES) approaches related to the visual system, and many of the technical considerations regarding fabrication, biocompatibility, stimulation thresholds and electrotoxicity. This review will address a principal outstanding question in retinal prosthesis development: the design and implementation of a functional interface with the retina. A functional interface between electrodes and retinal neurons will be stable, biocompatible, and will convey useful information to the visual system. Several parameters related to both the artificial and biological aspects of the interface must be considered; this paper will emphasize electrode design. Additional issues central to the development of prosthesis interface design, including retinal physiology, eye diseases, and existing animal models of retinal degeneration, are also summarized.

Animals↗

PubMedDate not supplied

Subretinal implantation of semiconductor-based photodiodes: durability of novel implant designs.

Selective degeneration of the retinal photoreceptor layers underlies blindness in retinitis pigmentosa (RP) and other inherited retinal disorders. Because there are no therapies for these patients, we are evaluating the possibility that electrical stimulation delivered to the subretinal space by a microphotodiode array (MPA) could replace, in some aspect, the function of diseased photoreceptors. Early MPA prototypes utilized gold as the electrode material, which gradually dissolved during the postoperative period following subretinal implantation. Here we present the results obtained when different MPA materials were used. Semiconductor-based silicon MPAs (2 mm in diameter; 50 microm in thickness), incorporating iridium/iridium oxide (IrOx) or platinum (Pt) electrodes, were implanted into the subretinal space of the right eye of normal cats with the use of vitreoretinal surgical techniques. Indirect ophthalmoscopy, fundus photography, ganzfeld electroretinography, and histology were used for the evaluation of the implanted retinas postoperatively. Infrared (IR) stimulation was used to isolate electrical responses generated by the MPA. The unimplanted left eyes were used for control purposes. After the implantation surgery, subretinal MPAs retained a stable position in the subretinal space. Up to 12 months after surgery, there was little change in the magnitude of the electrical response of IrOx- and Pt-based MPAs to a standard IR light stimulus. Overlying the implant, there was a near-complete loss of the outer retinal layer, which is likely to reflect obstruction of choroidal nourishment to these layers by the solid disk implant. In addition, the inner retinal layers showed variable disorganization. Away from the implant, the retina displayed a normal appearance. In comparison to electroretinograms (ERGs) obtained from unimplanted eyes, responses recorded from implanted eyes had a normal waveform but were slightly smaller in amplitude. These results indicate that IrOx and Pt improve implant electrode durability and that implants incorporating these materials into the electrode layer do not induce panretinal abnormalities.

Animals↗