Aart Kooijman

In Vitro and In Vivo Characterization of Pigment Epithelial Cells Differentiated from Primate Embryonic Stem Cells

PURPOSE To determine whether primate embryonic stem (ES) cell-derived pigment epithelial cells (ESPEs) have the properties and functions of retinal pigment epithelial (RPE) cells in vitro and in vivo. METHODS Cynomolgus monkey ES cells were induced to differentiate into pigment epithelial cells by coculturing them with PA6 stromal cells in a differentiating medium. The expanded, single-layer ESPEs were examined by light and electron microscopy. The expression of standard RPE markers by the ESPEs was determined by RT-PCR, Western blot, and immunocytochemical analyses. The ESPEs were transplanted into the subretinal space of 4-week-old Royal College of Surgeons (RCS) rats, and the eyes were analyzed immunohistochemically at 8 weeks after grafting. The effect of the ESPE graft on the visual function of RCS rats was estimated by optokinetic reflex. RESULTS The expanded ESPEs were hexagonal and contained significant amounts of pigment. The ESPEs expressed typical RPE markers: ZO-1, RPE65, CRALBP, and Mertk. They had extensive microvilli and were able to phagocytose latex beads. When transplanted into the subretinal space of RCS rats, the grafted ESPEs enhanced the survival of the host photoreceptors. The effects of the transplanted ESPEs were confirmed by histologic analyses and behavioral tests. CONCLUSIONS The ESPEs had morphologic and physiological properties of normal RPE cells, and these findings suggest that these cells may provide an unlimited source of primate cells to be used for the study of pathogenesis, drug development, and cell-replacement therapy in eyes with retinal degenerative diseases due to primary RPE dysfunction.

Light distribution on the retina of a wide-angle theoretical eye

In a theoretical eye with spherical and aspheric surfaces, the retinal illumination is calculated if a Ganzfeld luminance field is used. The resulting retinal light distribution is nearly homogeneous over the whole retina. The homogeneity is not much influenced by the size of the optical surfaces. The corresponding retinal area and the luminous flux entering the eye are calculated as functions of the size of the visual field. The values of the length of the light path through the crystalline lens and of the angle of incidence on the retina are described as functions of the angle in the visual field.

Defects in RGS9 or its anchor protein R9AP in patients with slow photoreceptor deactivation

The RGS proteins are GTPase activating proteins that accelerate the deactivation of G proteins in a variety of signalling pathways in eukaryotes. RGS9 deactivates the G proteins (transducins) in the rod and cone phototransduction cascades. It is anchored to photoreceptor membranes by the transmembrane protein R9AP (RGS9 anchor protein), which enhances RGS9 activity up to 70-fold. If RGS9 is absent or unable to interact with R9AP, there is a substantial delay in the recovery from light responses in mice. We identified five unrelated patients with recessive mutations in the genes encoding either RGS9 or R9AP who reported difficulty adapting to sudden changes in luminance levels mediated by cones. Standard visual acuity was normal to moderately subnormal, but the ability to see moving objects, especially with low-contrast, was severely reduced despite full visual fields; we have termed this condition bradyopsia. To our knowledge, these patients represent the first identified humans with a phenotype associated with reduced RGS activity in any organ.

Guidelines for calibration of stimulus and recording parameters used in clinical electrophysiology of vision

In order to perform a technically adequate clinical electrophysiological procedure it is necessary to calibrate the stimulating and recording equipment. Published standards for the electroretinogram (ERG)[1], electro-oculogram (EOG)[2], visual evoked potential (VEP)[3], and guidelines for the Pattern ERG (PERG)[4] specify stimulus and recording parameters. Yet, most commercial instruments do not provide the means for calibration of these parameters. The goal of this document is to provide guidelines for proper calibration of stimulus and recording equipment. The need for such guidelines is clear on both clinical and scientific grounds. Stimulus and amplifier characteristics have substantial effects on the peak latency and amplitude measurements that are commonly used in clinical electrophysiology. Many review articles on clinical electrophysiology emphasize the need for establishing norms for each laboratory as a function of age and gender rather than relying on published norms. However, if stimulus and recording parameters are not calibrated periodically, then these norms may actually be misleading due to changes in stimulus or recording conditions induced by aging of equipment or inadvertent change in settings.This document is divided into two major sections. The first is concerned with calibration of the visual stimulus. It begins with background technical information on the physics of light and its measurement. This is followed by protocols for measurement of the luminous intensity of flash stimuli and the mean luminance, contrast, and visual angle of pattern stimuli. The second section is concerned with calibration of electrophysiologic recording systems. It begins with a description of the characteristics of bioelectrical signals and their measurement. This is followed by protocols for measurement of electrode impedance and amplifier calibration. Although this document was prepared as guidelines for clinical electrophysiological testing, it should be noted that the techniques described are more generally applicable to studies which are dependent upon accurate measurement of luminance or electrophysiological signals.

The relationship of functional limitations to disability and the moderating effects of psychological attributes in community-dwelling older persons

This paper examines the moderating effects of three psychological attributes (neuroticism, self-efficacy expectancies and mastery) on the association between functional limitations (motor and cognitive limitation, vision and hearing loss) and disability ((instrumental) activities of daily living, role function and social function) in a sample of 624 community-dwelling older persons. In contrast to our hypothesis, we did not find any evidence for interaction effects. This means that low levels of psychological resources do not exacerbate the effect of functional limitation on disability in community-dwelling older persons. We found significant unique contributions of the psychological attributes to disability. Even when all three psychological attributes were taken into account, neuroticism and mastery had unique effects on social and role function, and self-efficacy expectancies had unique effects on (instrumental) activities of daily living. We conclude that the effects of functional limitation and psychological attributes on disability can be considered as additive. Older persons with less psychological resources are particularly at risk in developing disability.

Spherical and irregular aberrations are important for the optimal performance of the human eye.

Contrast sensitivity measured psychophysically at different levels of defocus can be used to evaluate the eye optics. Possible parameters of spherical and irregular aberrations, e.g. relative modulation transfer (RMT), myopic shift, and depth of focus, can be determined from these measurements. The present paper compares measured results of RMT, myopic shift, and depth of focus with the theoretical results found in the two eye models described by Jansonius and Kooijman (1998 ). The RMT data in the present study agree with those found in other studies, e.g. Campbell and Green (1965 ) and Jansonius and Kooijman (1997 ). A new theoretical eye model using a spherical aberration intermediate between those of the eye models described by Jansonius and Kooijman (1998 ) and an irregular aberration with a typical S.D. of 0.3–0.5 D could adequately explain the measured RMT, myopic shift, and depth of focus data. Both spherical and irregular aberrations increased the depth of focus, but decreased the modulation transfer (MT) at high spatial frequencies at optimum focus. These aberrations, therefore, play an important role in the balance between acuity and depth of focus.

Age-related changes of defocus-specific contrast sensitivity in healthy subjects.

To investigate the effect of defocus on contrast sensitivity as a function of age in healthy subjects, the through focus contrast sensitivity was measured in 100 healthy subjects aged 20–69. Defocus‐specific changes in contrast sensitivity reflect age‐related changes in the optics of the eye. Tests were performed in cycloplegic eyes varying artificial pupil size (2, 4 and 6 mm), defocus (−1 to +2 D), and spatial frequency (1–16 cpd). Integrated contrast sensitivity was taken as a measure for the total amount of visual information transferred by the optical media.

Effect of intraocular lens implantation on visual acuity, contrast sensitivity, and depth of focus

Purpose: To determine the role of spherical and irregular aberrations in the optics of the natural eye and after intraocular lens (IOL) implantation in terms of visual acuity, contrast sensitivity, and depth of focus. Setting: Laboratory of Experimental Ophthalmology, University of Groningen, Groningen, The Netherlands. Methods: Visual acuity and defocus‐specific contrast sensitivity in 11 pseudophakic patients (IOL group) and 27 age‐matched phakic subjects were compared. The results were obtained psychophysically. Spherical and irregular aberrations were subsequently estimated by comparing the measured myopic shift (optimum focus of contrast sensitivity at 4 cycles per degree [cpd] compared to that at 16 cpd) and depth of focus with those of theoretical eye models with varying amounts of irregular and spherical aberrations. Results: The best corrected visual acuity and best corrected contrast sensitivity in the IOL group did not significantly differ from that in the phakic group. The depth of focus was larger in the IOL group at a pupil diameter of 6.0 mm (P<.05). Comparison with theoretical eye models suggested a higher amount of spherical aberration in the IOL group; irregular aberration was almost the same in both groups. Conclusions: There was a higher amount of spherical aberration in the IOL group, related to a larger depth of focus, without loss of contrast sensitivity at optimum focus or loss of visual acuity. This might contribute to better quality of vision in pseudophakic subjects than in presbyopic phakic subjects.

Effect of methods of myopia correction on visual acuity, contrast sensitivity, and depth of focus

Purpose: To psychophysically measure spherical and irregular aberrations in patients with various types of myopia correction. Setting: Laboratory of Experimental Ophthalmology, University of Groningen, Groningen, The Netherlands. Methods: Three groups of patients with low myopia correction (spectacles, soft contact lens, and Intacs) and 4 groups with high myopia correction (spectacles, rigid contact lens, Artisan claw lens, and laser in situ keratomileusis [LASIK]) had through‐focus contrast sensitivity measurements to establish the myopic shift and depth of focus. From these 2 parameters, spherical and irregular aberrations were determined using theoretical eye models and geometric optics. Visual acuity, stray light, and predictability were also studied. Results: There were no differences in best corrected visual acuity (BCVA) or best corrected contrast sensitivity between the low myopia groups. The Intacs group had a significantly larger depth of focus (P<.05). The results in the soft contact lens group were comparable to those in a human eye model with an average amount of spherical and irregular aberrations. The LASIK group had worse uncorrected visual acuity (UCVA) and best corrected contrast sensitivity than the spectacles, rigid contact lens, and Artisan claw lens groups (P<.05) due to the amount of spherical and irregular aberrations present after LASIK. The low and high myopia spectacles groups had average amounts of spherical and irregular aberrations. Conclusions: Neither surgical techniques nor contact lenses resulted in BCVA or best corrected contrast sensitivity that surpassed the values measured in the best corrected spectacles groups. The Artisan claw lens performed better than LASIK in UCVA, predictability, and best corrected contrast sensitivity.

Does visual impairment lead to additional disability in adults with intellectual disabilities

BACKGROUND This study addresses the question to what extent visual impairment leads to additional disability in adults with intellectual disabilities (ID). METHOD In a multi-centre cross-sectional study of 269 adults with mild to profound ID, social and behavioural functioning was assessed with observant-based questionnaires, prior to expert assessment of visual function. With linear regression analysis the percentage of variance, explained by levels of visual function, was calculated for the total population and per ID level. RESULTS A total of 107/269 participants were visually impaired or blind (WHO criteria). On top of the decrease by ID visual impairment significantly decreased daily living skills, communication & language, recognition/communication. Visual impairment did not cause more self-absorbed and withdrawn behaviour or anxiety. Peculiar looking habits correlated with visual impairment and not with ID. In the groups with moderate and severe ID this effect seems stronger than in the group with profound ID. CONCLUSION Although ID alone impairs daily functioning, visual impairment diminishes the daily functioning even more. Timely detection and treatment or rehabilitation of visual impairment may positively influence daily functioning, language development, initiative and persistence, social skills, communication skills and insecure movement.