Biomedical subjects

B Ehinger

Publications and source records attributed to B Ehinger.

At least 37 records · Page 2Linked to original sources

PubMed1999

Nitric oxide-producing cells project from retinal grafts to the inner plexiform layer of the host retina.

PURPOSE: Amacrine cells expressing nitric oxide synthase (NOS) are seen in normal retinas and retinal grafts to extend long processes, which can be followed for long distances. Taking advantage of the morphologic features of these cells, the present study examined whether graft-host connections involve cells capable of producing nitric oxide, a recognized retinal neuromodulatory compound. METHODS: Embryonic day 15 rabbit retinas were transplanted to the subretinal space of adult rabbits. The localization of the neuronal form of NOS was assessed by immunocytochemistry in grafts that had reached the equivalent ages of postnatal days 5, 12, 20, 45, 90, and 102. RESULTS: NOS-containing cells and processes were seen in all the transplants. Processes were found to project mainly toward areas within the graft. Yet, at all survival times examined, single immunolabeled fibers could be seen to cross the graft- host border. In fortuitous cases, it was possible to establish that the bridging fiber originated in the graft. Further, bridging fibers were seen to reach the NOS-immunolabeled host inner plexiform layer. CONCLUSIONS: Graft NOS-containing cells are not only capable of projecting into the host but also of reaching the appropriate target for NOS-containing fibers within the host retina. This indicates that at least some graft-host connections are established by graft cells that retain their ability to synthesize a modulatory compound and which potentially could contact their partner cells in the host retina.

Animals↗

PubMed1999

Graft-host connections in long-term full-thickness embryonic rabbit retinal transplants.

PURPOSE: To establish neuronal connections in the rod and cone pathway between laminated rabbit retinal transplants and the host retina. METHODS: Fourteen adult rabbits received a complete full-thickness embryonic transplant. After survival times of 3 to 10 months, the retinas were studied under light microscope and with immunohistochemistry. Antibodies against protein kinase C (PKC), parvalbumin, and calbindin were used to label rod bipolar cells, AII amacrine cells, and cone bipolar cells, respectively. The AB5 antibody was used to label ganglion cells. RESULTS: The transplants displayed laminated morphology with layers parallel to the host retinal pigment epithelium. In the oldest specimens (10 months after surgery), laminated layers of graft and host approached each other and almost reconstructed the normal retinal appearance. The ganglion and cone bipolar cells of the host survived well, as was seen with AB5 and calbindin double-labeling. Connections between cone bipolar cells in the graft and ganglion cells in the host were not common. PKC-labeled rod bipolar cells and parvalbumin-labeled AII amacrine cells of host and graft showed sprouting activity directed toward an intermediate plexiform layer located between the graft and host. In specimens double-labeled with PKC and parvalbumin, this intermediate plexiform layer was seen to contain numerous PKC- and parvalbumin-labeled processes. Direct connections between rod bipolar and AII amacrine cells in host and graft were seen in the 10-month specimens. CONCLUSIONS: Full-thickness embryonic transplants survive for at least 10 months, and normal laminated morphology develops. Host and graft fuse and together contribute nerve cell processes to an intermediate plexiform layer. Direct graft-host contacts are also present between neuronal types that in the normal retina participate in the rod pathway.

Animals↗

PubMed1999

Long-term full-thickness embryonic rabbit retinal transplants.

PURPOSE: To establish the light and electron microscopic morphology of long-term full-thickness embryonic rabbit retinal transplants, with special attention paid to graft- host integration. METHODS: Eighteen rabbits received a complete embryonic neuroretina 19 days after conception. The transplants were positioned under the host retina, flat against the host retinal pigment epithelium with proper polarity, using a vitrectomy technique. After surviving 3 to 10 months, the transplants were examined by light and electron microscopy. RESULTS: The outer retina of the host had degenerated in all specimens. In 16 of the 18 eyes, well-laminated transplants with correct polarity, measuring up to 3.2 mm in length, were found. The transplants displayed long outer segments facing the host retinal pigment epithelium, and they were laminated to the level of the inner plexiform layer in which fusion with the host was often evident. Fusion was more prominent in the oldest transplants. Electron microscopy revealed bundles of neurites at different levels of maturation in close contact with Müller cell fimbriae at regular intervals along the graft-host border. CONCLUSIONS: Full-thickness embryonic rabbit retinal transplants positioned with correct polarity develop into large laminated retinas and survive without immunosuppression for at least 10 months. Host and graft adapt and almost reconstruct the normal retinal appearance. Ultrastructurally, well-developed photoreceptors and many normal synapse types are seen, and neuron sprouting is evident at the graft-host border.

Animals↗

PubMed1998

Correlations between cholinergic neurons and muscarinic m2 receptors in the rat retina.

Acetylcholine is well established as the neurotransmitter of starburst amacrine cells in the vertebrate retina but their function is poorly understood. We compared the distribution of muscarinic m2 receptors in the rat retina with the localization of the starburst cell processes. mAChR2 immunoreactivity appeared in a central band in the inner plexiform layer, which did not co-localize with the processes of the cholinergic amacrine cells. We found co-labelling of VAChT and ChAT making it highly unlikely that there are undetected cholinergic neurons in rat retina. Most mAChR2 receptors were located far from the cholinergic neurons, suggesting that most of them are unlikely to be associated with conventional cholinergic synapses.

Acetylcholine↗

PubMed1998

Gamma-aminobutyric acidA receptors on a bistratified amacrine cell type in the rabbit retina.

Gamma-Aminobutyric acid (GABA) is considered to be a major inhibitory neurotransmitter in the inner plexiform layer of the retinas of all vertebrate species. It is contained in and released from nearly 40% of the amacrine cells and is known to play a major role in many aspects of visual processing. By using well-characterized antibodies to several subunits of the GABA(A) receptor, we have analyzed their localization on the cell bodies and dendritic trees of two amacrine cell populations in the rabbit retina, which have been either filled intracellularly with Lucifer yellow or stained immunohistochemically. Both populations are selectively stained by intravitreal injection of the fluorescent nuclear dye 4',6-diaminidin-2-phenylindoldihydrochloride (DAPI). We have found that the most significant concentration of the alpha1 and beta2/3 GABA(A) receptor subunits is localized to the DAPI-3 type amacrine cell. The perikarya of the DAPI-3 cells are found in the proximal inner nuclear layer and send their processes into two sublayers in sublaminae a and b of the inner plexiform layer. These processes abut but do not directly overlap those of the two mirror-symmetric populations of starburst amacrine cells. Because the cell bodies of the DAPI-3 cells are the only ones in the inner nuclear layer that stain strongly for either the alpha1 or beta2/3 subunits, such staining is a diagnostic feature of these cells. Their processes also constitute the most strongly staining ones found within the inner plexiform layer. The dendritic trees of DAPI-3 cells, which range from about 150 microm up to about 300 microm, exhibit recurvate looping processes reminiscent of those described for directionally selective ganglion cells. In contrast to the DAPI-3 cell, we have also shown that the starburst amacrine cells exhibit no immunoreactivity for the alpha1 GABA(A) receptor subunit and very little for the beta2/3 subunit. Thus, we have shown that the DAPI-3 cells contain the highest concentrations of the alpha1 and beta2/3 GABA(A) receptor subunits in the rabbit retina. These cells, which costratify near the processes of both the starburst amacrine cells and the ON-OFF directionally selective ganglion cells, thus, are situated both anatomically and by virtue of their receptor content to potentially interact.

Animals↗

PubMed1998

Endogenous hyaluronan in the normal and traumatized rabbit iris.

PURPOSE: Hyaluronan concentration in the iris tissue after iridectomy was studied in order to establish the influence of trauma on the production of hyaluronan in the anterior chamber of the eye and whether the iris participates in this process or not. METHOD: Hyaluronan was measured with a radiometric assay at different time points after surgery and identified with specific histochemical staining. RESULTS AND CONCLUSIONS: The concentration of hyaluronan in iris tissue peaked two days after surgery, reaching an average of 115.3 (S.E.M.:+/-12.2) microg/g. It then decreased slowly to almost normal values after 3 to 5 weeks. Histochemistry demonstrated the most intense hyaluronan staining in the iris stroma and in iridial processes around the iridectomy two days after the operation. Our findings indicate in situ synthesis of hyaluronan in the iris tissue.

Animals↗

PubMed1998

Survival and MHC-expression of embryonic retinal transplants in the choroid.

PURPOSE: To study the survival of syngenic versus allogenic embryonic retinal transplants in the choroid, and try to correlate the survival to the expression of MHC-expression and the presence of activated microglia. METHOD: Fetal neural retinas of Sprague-Dawley (SD) rats were implanted in the choroid of adult Lewis and SD rats. After 3 weeks the retina, the choroid and the transplants were examined by light microscope and evaluated with antibodies against MHC class I and II. RESULTS: Retinal transplants were found in all eyes. The transplants had one subretinal and one choroidal component. The syngenic transplants thrived in the subretinal space and formed rosettes and the choroidal components had to some extent rosette formation, though not as distinct as in the subretinal part. Almost no upregulation of MHC class I and II was seen. The allogenic transplants were totally deranged in the subretinal space as well as in the choroid. There was a marked upregulation of MHC class I, most pronounced in the transplants, but also in the host retina. Numerous MHC class II positive cells were seen in the transplants, but also in the host retina. All of these cells were dendritic and had the typical appearance of microglia. CONCLUSION: Syngenic choroidal transplants were seen to grow and thrive, whereas the allogenic transplants were rejected. There is a considerable upregulation of MHC expression in the allogenic transplants, but not in the syngenic.

Animals↗

PubMed1998

The expression of GABA(A) receptors during the development of the rabbit retina.

PURPOSE: Gamma-amino butyric acid (GABA) is a major inhibitory neurotransmitter in the retina, possibly participating in its normal development. The distribution of gamma-aminobutyric acid receptors was therefore examined in mature and developing rabbit retina by GABA(A) receptor alpha1 and beta2/3 subunit immunocytochemistry. RESULTS: Beta2/3 subunits appeared already at the E25 stage (25 days after gestation) although only weakly and irregularly. Alpha1 subunit immunoreactivity was first observed at birth. On the fifth postnatal day, immunostaining was clearly seen in the inner plexiform layer, and weaker, in the outer plexiform layer. There were at this stage no well-delineated sublayers in either the inner or the outer plexiform layer, but three clearly defined sublayers appeared in the inner plexiform layer at PN10. Amacrine cell bodies now also appeared, labelling for both the GABA(A) receptor alpha1 and the beta2/3 chains. A punctuate labelling appeared in the outer plexiform layer. From the 20th postnatal day, the immunoreactivity was similar to that seen in adult rabbits. CONCLUSIONS: Like in the adult, the alpha1 and beta2/3 subunits of the GABA(A) receptor thus colocalize predominantly in certain amacrine cells and in processes of the inner plexiform layer during the development of the retina. The GABA(A) receptors appear later than GABA during the development of the rabbit retina, and functioning GABA neurotransmitter circuits appear to be assembled primarily after the 3rd to 5th postnatal day. Our results support the hypothesis that GABA may have other functions than mediating classic synaptic neurotransmission before the formation of receptors containing the alpha1 and beta2/3 subunits. Like in the brain, the alpha subunits may have more selective functions during the development than the beta subunits.

Animals↗

PubMed1998

Phenotypic expression of autosomal dominant retinitis pigmentosa in a Swedish family expressing a Phe-211-Leu variant of peripherin/RDS.

PURPOSE: To characterize the clinical phenotype, with emphasis on electrophysiology, of members of a Swedish family with autosomal dominant retinitis pigmentosa due to a novel mutation, F211L, in the peripherin/RDS gene. METHODS: Nine patients with autosomal dominant retinitis pigmentosa and two healthy family members underwent a full clinical evaluation including kinetic visual field testing, measurement of dark adaptation threshold, and full-field electroretinography. Blood samples were collected and DNA analysis was performed using denaturing gradient gel electrophoresis (DGGE). RESULTS: The grandfather, six of seven siblings from the middle generation, and two young boys carried the mutation F211L in the peripherin/RDS gene. The mutation segregated with the clinical presentation of disease. Fundus examination revealed mainly macular atrophy. All assessed parameters of retinal function (visual acuity, dark adaptation threshold, visual fields, and full-field electroretinograms) demonstrated a successive reduction with increasing age. Full-field electroretinograms showed a diminished rod response in all affected individuals and a reduction of the cone b-wave amplitudes with increasing age, indicating retinitis pigmentosa. In the affected family members, the disease seems to progress at a similar rate with increasing age. CONCLUSIONS: The peripherin/RDS gene mutation F211L is associated with a clinical phenotype and includes early loss of rod function and successive reduction of cone function with increasing age, but impressively well-preserved visual acuity and visual fields in young and middle-aged patients and moderately reduced vision in the old patient. Compared to previously described phenotypes segregating with mutations in the peripherin/RDS gene, the present family demonstrates a more benign clinical phenotype, which is concordant within the family.

Adolescent↗

PubMed1998

A Swedish family with a mutation in the peripherin/RDS gene (Arg-172-Trp) associated with a progressive retinal degeneration.

PURPOSE: To clinically characterize a Swedish family with autosomal dominant retinitis pigmentosa due to a mutation, Arg-172-Trp, in the peripherin/RDS gene. METHODS: Full clinical evaluation including kinetic visual field testing, measurement of dark-adaptation threshold, and full-field electroretinography in seven patients with autosomal dominant retinitis pigmentosa and three healthy family members. Denaturing gradient gel electrophoresis (DGGE) was used for mutation screening in seven patients and six healthy members of the family. RESULTS: Three of four siblings from the middle generation and four of the younger generation were heterozygous for the peripherin /RDS Arg-172-Trp mutation. The mutation segregated with the disease. Visual acuity decreased progressively with age and visual fields were moderately constricted in young patients, while central scotoma and constriction of the fields were detected in the family members above 50 years of age. The results from full-field electrography were comparable with a widespread retinal degeneration. CONCLUSIONS: Earlier, the peripherin/RDS Arg-172-Trp mutation was associated primarily with a macular degeneration phenotype. One previous study indicated that this mutation also can give rise to a degeneration of the more peripheral parts of the retina. In the present study, a widespread retinal degeneration is seen in the patients above 50 years of age, carrying the Arg-172-Trp mutation.

Adult↗

PubMed1998

Clinical expression of X-linked retinitis pigmentosa in a Swedish family with the RP2 genotype.

PURPOSE: To examine the clinical phenotype with emphasis on electroretinograms and visual fields in a Swedish family with X-linked retinitis pigmentosa (XLRP) type 2 (RP2), and compare it with Swedish XLRP families with the RP3 genotype. METHODS: Three affected brothers and their carrier mother were examined clinically and with kinetic perimetry, dark adaptation thresholds, and full-field electroretinograms. The genotype was determined by haplotype analysis using polymorphic markers spanning the XLRP loci at the short arm of the X chromosome. RESULTS: The phenotype was consistent in the three affected males. The first subjective symptom was night blindness and the visual disability was more pronounced with increasing age. Affected individuals had a slight decrease in visual acuity and were emmetropic. They demonstrated a pathologically elevated final rod threshold. The visual fields were constricted in a somewhat atypical pattern. The three patients had an early presenting atypical cataract with multiple opacities. The fundus appearance was typical for RP with narrowing of retinal vessels and bone spicule pigmentations. The rod electroretinograms were extinguished in both eyes of the patients. The combined rod-cone responses as well as the isolated cone responses were severely reduced in amplitude; however, atypically for RP, the implicit time for the isolated cone responses was normal. The carrier female demonstrated normal ophthalmological findings, with the exception of two minimal pigmentations in the lower quadrants of the left eye. Haplotype analysis demonstrated that the disease in this family segregates with the RP2 locus. CONCLUSION: The phenotype of the studied RP2 family is associated with early onset of night blindness, emmetropia, a slight decrease in visual acuity, constriction of visual fields, and atypical cataract formation. Electroretinograms demonstrate severe rod dysfunction and surprisingly normal cone response implicit times which may indicate a milder disease progression. These findings are different from earlier descriptions of the RP2 and RP3 phenotypes.

Adolescent↗

PubMed1998

Transplant of full-thickness embryonic rabbit retina using pars plana vitrectomy.

PURPOSE: To develop an improved surgical technique making full-thickness retinal transplant possible, thereby achieving a normal laminated transplant with minimal rosette formation. METHODS: A total of 23 rabbits underwent vitrectomy, retinotomy, and subsequent subretinal transplant of a complete embryonic neuroretina using a specially crafted glass cannula. Of the 23 animals, 15 received a prenatal day 16 or 19 (E16 or E19) retina; the remaining eight received an E15 retina. The animals were followed from 10 to 35 days, and after this period, the transplants were sectioned and stained for light microscopy. RESULTS: In 11 of the 15 transplants with E16 or E19 donors, histology showed regions up to 1.8 mm of straight, correctly positioned transplants with layering corresponding to their age. The eight animals kept alive longest postoperatively, 31 or 35 days, all showed normal retinal layers, including photoreceptor outer segments appositioned against the host retinal pigment epithelium. Tissue from the youngest donors (E15) yielded less well-organized transplants, indicating a critical stage in retinal embryogenesis before which transplant in this respect is less favorable. CONCLUSIONS: Our procedure makes it possible to transplant embryonic retina to the appropriate position adjacent to the host retinal pigment epithelium, keeping the transplant architecture intact. The transplants show good layering and well-developed photoreceptors abutting the retinal pigment epithelium.

Animals↗

PubMed1998

Detection of alterations in all three exons of the peripherin/RDS gene in Swedish patients with retinitis pigmentosa using an efficient DGGE system.

AIMS: To develop a sensitive mutation screening procedure suitable for routine analysis of the peripherin/RDS gene, and to estimate the nature and prevalence of peripherin/RDS gene mutations in Swedish patients with autosomal dominant retinitis pigmentosa. METHODS: To make the method as sensitive as possible, as many as eight segments, covering the three exons and the flanking intron sequences of the peripherin/RDS gene, were analysed by denaturing gradient gel electrophoresis. A group of 38 Swedish patients with a clinical diagnosis of autosomal dominant retinitis pigmentosa were screened for mutations in the peripherin/RDS gene. RESULTS: Three point mutations were found in four of the patients and five polymorphisms were defined. One mutation in exon 1, R172W, has been described previously in other ethnic groups as causing a macular degeneration. Another mutation, in exon 2 and causing the substitution F211L, was found in two unrelated patients. A third mutation, resulting in the likely non-pathogenic substitution S289L, as well as a polymorphism not reported previously, was found in exon 3. CONCLUSIONS: The screening procedure described allows detection of mutations in all of the exons, including the polymorphic 5' and 3' ends of the gene, and is therefore suitable for routine screening of peripherin/RDS gene defects in patients with autosomal dominant retinitis pigmentosa. The frequency of mutations found in the Swedish patient group indicates that defects in the peripherin/RDS gene might be a more common cause of autosomal dominant retinitis pigmentosa than was thought previously.

Electrophoresis↗

PubMed1998

Phenotype of an X-linked retinitis pigmentosa family with a novel splice defect in the RPGR gene.

PURPOSE: To assess the clinical phenotype in a Swedish family with X-linked retinitis pigmentosa (XLRP) resulting from a novel splice defect in the RPGR gene. METHODS: RPGR mutation analysis was performed in one family with XLRP, and several individuals from the family were examined clinically. RESULTS: The causative mutation in the family was demonstrated to be a single base-pair change at the splice donor site in intron 7 that resulted in skipping of the complete exon 7 in the mature RPGR transcript. The aberrant mRNA is predicted to produce an RPGR protein with an in-frame deletion of 53 amino acids, corresponding to an RCC1-homology repeat. Clinical studies that included ophthalmological examination and full-field electroretinography showed that this splice mutation resulted in a comparatively less severe form of RP. CONCLUSIONS: Correlation of a causative RPGR genotype with clinical findings in hemizygotes and carrier heterozygotes is an important step toward predictive diagnosis and should assist in the development of gene-based therapies in the future.

Carrier Proteins↗

PubMed1997

Mitosis in developing rabbit retina: an immunohistochemical study.

The proliferation of cells in the embryonic and postnatal rabbit retina was studied with the MIB-1 antibody which demonstrates the Ki-67 antigen. Already at embryonic day 15 there were postmitotic cells (i.e. cells that do not stain with the MIB-1 antibody) in the basal part of the neuroblastic cell mass which are presumably the differentiating ganglion cells. After the formation of an inner plexiform layer at around embryonic day 25, postmitotic cells were seen in the proximal part of neuroblastic cell mass (presumably amacrine cells) as well as in the ganglion cell layer. Proliferating cells accumulated distal to the layer of postmitotic cells and their number gradually decreased towards the pigmented epithelium. At birth, proliferation ceased in the central parts of the retina but in the peripheral parts it continued for 7 days although rare cells could be seen for up to 15 days. After the formation of the outer plexiform layer, the proliferating cells in the outer nuclear layer accumulated close to the outer plexiform layer whereas the postmitotic cells (the differentiating photoreceptors) did so at the distal part of outer nuclear layer. Some cells in the middle of the inner nuclear layer (presumably the Müller cells) and some cells in the ganglion cell layer or nerve fiber layer (presumably the astrocytes) proliferated for the longest period of time.

Animals↗

PubMed1997

Immunocytochemical localisation of neuronal nitric oxide synthase in developing and transplanted rabbit retinas.

Nitric oxide (NO) acts as a modulator of neuronal transmission in mature neuronal systems, including the retina. Recently, NO has also been suggested to have a trophic function during development. We examined immunocytochemically the distribution of NO-producing cells in developing and transplanted rabbit retinas. An antibody detecting the neuronal isoform of its biosynthetic enzyme, nitric oxide synthase (NOS), was used on normal developing retinas [starting at embryonic day (E) 15] and on rabbit retinal transplants after various survival times (1-139 days after surgery). Weakly stained cell bodies were first observed in the proximal margin of the neuroblastic layer at E 29. Stained processes projecting towards a developing inner plexiform layer were also visible at this time point. Immunoreactive cells were located at later stages in the innermost part of the inner nuclear layer and in the ganglion cell layer, and are likely to correspond mainly to amacrine cells. NOS-labelled cells were also found in retinal transplants. The first NOS-labelled cells appeared, as in normal developing retinas, in ages corresponding to E 29 and were still detected in transplants corresponding to postnatal day 123. NOS-labelled cells were seen in areas between rosettes, where amacrine cells are located. NOS-labelled processes were at times seen to project for long distances, forming very distinct plexuses. NOS-containing amacrine cells thus appear both in the transplants and in developing retinas in the embryonic stages, long before synaptic function involving these cells can be expected, suggesting a role for NO not only in neuromodulation but also in retinal development.

Age Factors↗

PubMed1997

Phenotypes in three Swedish families with X-linked retinitis pigmentosa caused by different mutations in the RPGR gene.

PURPOSE: To assess the clinical phenotypes in three Swedish families with X-linked retinitis pigmentosa caused by different mutations in the RPGR gene. METHODS: Three families from different parts of Sweden, including nine patients with retinitis pigmentosa and six female carriers of X-linked retinitis pigmentosa, were examined clinically. Ophthalmologic examination included kinetic perimetry with a Goldmann perimeter using standardized objects I4e and V4e, dark adaptation final thresholds with a Goldmann-Weeker adaptometer, and full-field electroretinograms. RESULTS: The clinical findings in the patients demonstrated a severe form of retinitis pigmentosa with visual handicap early in life. Patients with a microdeletion of exons 8 through 10 of the RPGR gene had a more severe phenotype compared to the patients with single base-pair mutations in the introns 10 and 13 of the RPGR gene, resulting in splicing defects. Furthermore, heterozygous carriers in these families displayed a wide spectrum of clinical features, from minor symptoms to severe visual disability. CONCLUSION: These three families show a variable clinical phenotype resulting from different mutations in the RPGR gene. A microdeletion spanning at least parts of exons 8 through 10 seems to result in a severe phenotype compared to the splice defects. Heterozygous carriers of X-linked retinitis pigmentosa with these specific RPGR genotypes also show a variability of the phenotype; carriers with the microdeletion may be severely visually handicapped.

Adolescent↗

PubMed1997

Autosomal dominant retinitis pigmentosa with a rhodopsin mutation (Arg-135-Trp). Disease phenotype in a Swedish family.

We here present the clinical phenotype in 6 patients from a family with autosomal dominant retinitis pigmentosa found to carry a point mutation in the rhodopsin gene (arginine-135-tryptophan). The mutation is the second found by mutation screening of DNA from 20 Swedish families with dominant retinitis pigmentosa. With full-field electroretinography we could document a severe form of retinitis pigmentosa in patients belonging to the family, similar to the phenotype associated with the previously reported mutation (arginine-135-leucine). Our results indicate that different point mutations in the same region of the rhodopsin gene, resulting in amino acids with similar properties (both hydrophobic), may cause a similar clinical phenotype. Further, point mutations in this specific region seem to cause an agressive form of retinitis pigmentosa.

Adolescent↗