Search PubMed⌕ Search

Biomedical subjects

L H Pinto

Publications and source records attributed to L H Pinto.

At least 55 records · Page 3Linked to original sources
PubMed1991

The potassium channel MBK1 (Kv1.1) is expressed in the mouse retina.

1. The neurons of the retina have electrical properties that are different from those of most of the other neurons of the central nervous system. To identify the voltage-gated ion channels found in the retina, we screened mouse retinal cDNA libraries with oligonucleotide probes homologous to the mammalian K+ channel MBK1 (Kv1.1) and ligated two partial clones to produce a full-length clone with no significant differences from MBK1. 2. Expression of MBK1 mRNA was determined by RNAse protection. MBK1 mRNA was detected in retinal RNA and was also detected in brain, liver, and heart RNAs. 3. We transcribed the full-length clone, injected it into oocytes of Xenopus laevis, and measured the membrane currents 2 to 6 days later. Depolarization from a holding voltage of -90mV induced a slowly activated outward current with a peak value as large as 20 microA. The current inactivated very slowly with a single exponential time course [mean time constant, 6.5 +/- 0.4 sec (SEM) for activation voltage of -10mV]. 4. The outward current was reduced to half-maximal by 0.42 mM tetraethylammonium, 1.1 mM 4-aminopyridine, and 3.2 mM Ba2+ but was not significantly attenuated by Co2+ (1 mM). 5. The reversal potential (measured with tail currents) changed by 53mV per decade change of [K+] from 1 to 77 mM. 6. The voltage for half-maximal activation of the conductance was -26.6mV (+/- 1.7mV), and the voltage required for an e-fold increase in conductance was 6.9mV (+/- 0.5mV). 7. Thus, the mRNA for MBK1 found in the mouse retina causes the expression of a voltage-dependent K+ current which has properties suitable for may retinal neurons.

Animals↗
PubMed1991

Prospective randomized trial comparing hyperfractionated versus conventional radiotherapy in stages III and IV oropharyngeal carcinoma.

From April 1986 to May 1989, 112 patients seen at a single institution with previously untreated squamous cell oropharynx carcinoma, Stages III and IV, were randomly assigned to 66 Gy in 33 fractions of 2 Gy each (conventional RT) versus 70.4 Gy in 64 fractions of 1.1 Gy given twice a day with a minimal interfraction interval of 6 hours (hyperfractionated RT). The overall time for both arms was 6 1/2 weeks. Patients were stratified by site (base of the tongue vs others), T stage (T1/T2 vs T3 vs T4), N stage (N0/N1 vs N2 vs N3), and lymphnode size (less than 6 cm vs greater than 6 cm). As of January 1990, an analysis was performed in 98 patients (8 patients in the conventional arm and 6 in the hyperfractionation not included). The groups were balanced by age, performance status, stage, and site of the primary disease. The median follow-up time was 25 months. The probability of complete loco-regional response was 62% in the hyperfractionation arm and 52% for the conventional fractionation (p = 0.28). There was no difference in the control of lymphnodal disease (hyperfractionated = 55%, conventional = 57%; p = 0.92), but the disease control in the oropharynx only was significantly improved in the hyperfractionation arm (84% vs 64%, p = 0.02). Overall survival rate at 42 months was 27% for the hyperfractionation arm and 8% for the conventional (p = 0.03). Survival rates for hyperfractionated versus conventional RT were 40% versus 18% (p = 0.06), respectively, for Stage III patients and 16% versus 0% (p = 0.15), respectively, for Stage IV. There was significant improvement in survival in favor of the hyperfractionation arm in patients with lesions outside the base of the tongue (31% vs 15%, p = 0.02), for those with a 50-70% Karnofsky status (19% vs 0%, p = 0.006) and for patients with N0/N1 disease (38% vs 15%, p = 0.03). Acute toxicities were of similar magnitude, although both skin and mucosal reactions appeared earlier on the hyperfractionation scheme. To date, no differences in late toxicity have been observed. We conclude that in a subset group of patients with locally advanced carcinoma of the oropharynx, hyperfractionated radiotherapy appears to provide improved survival without adding to increased toxicity.

Adult↗
PubMed1991

Membrane currents and pharmacology of retinal bipolar cells: a comparative study on goldfish and mouse.

We obtained solitary bipolar cells using enzymatic (papain) dissociation of the goldfish and mouse (C57BL/6J, adult) retinae and measured the membrane currents of these cells by whole-cell patch clamp. Bipolar cells of these two species showed two main differences. A. Ca current 1. In the mouse, depolarization evoked a transient Ca current that had maximal amplitude at about -30 mV. 2. The Ca conductance was activated by voltage steps to potentials greater than -60 mV and inactivated fully at potentials greater than -20 mV. 3. The mouse Ca current was insensitive to Cd2+ or dihydropyridine. 4. Contrary to mouse, goldfish bipolar cells had a sustained Ca current, which was activated over a more positive potential range (greater than -30 mV), blocked by either 50 microM Cd2+ or 10 microM nifedipine, and markedly augmented by 10 microM Bay K8644. 5. The transient character of the Ca current in mouse bipolar cells may help to shape phasic responses of ganglion cells, while in goldfish the sustained nature of Ca current may contribute to shape tonic responses of ganglion cells. B. Pharmacology 1. We examined the effects of the inhibitory transmitters, glycine and GABA, on bipolar cells. 2. GABA produced strong inhibitory effects on bipolar cells of both goldfish and mouse. 3. The highest GABA sensitivity was found at the bipolar cell axon terminal, the site of reciprocal connection with amacrine cells. 4. GABA increased the Cl conductance. 5. Unlike GABA, glycine was effective only on the mouse bipolar cells. Axon terminals showed the highest glycine sensitivity. 6. Glycine-induced currents were also carried by Cl ions. 7. Since ECl in intact cells is assumed to be -55 mV, both GABA and glycine are thought to generate hyperpolarizing responses in cells maintained at their resting potential (ca. -45 mV). 8. The present study suggests that inhibition from amacrine cells to bipolar cells, found in both species, is mediated by different transmitters.

Animals↗
PubMed1991

Injection of RNA from carp retina induces the formation of a membrane potassium channel in Xenopus oocytes.

Total RNA was purified from freshly isolated retinas of adult carp and injected into oocytes of Xenopus laevis (stages 5-6). Two to six days after injection, depolarizing voltage-clamp steps evoked a slowly activated outward current as large as 3 microA. This current inactivated slowly with a single time constant (tau = 3.1 +/- 0.24 S.E.M., for Vm = +30 mV). The current was inhibited by tetraethylammonium (3.8 mM for half-maximal inhibition). In the presence of Co2+ (1 mM) or barium methanesulfonate (40 mM), the current-voltage relationship shifted to slightly more depolarized values (5-10 mV); the maximal value of the current that was sensitive to Co2+ or Ba2+ treatments was only a small fraction (about 10%) of the TEA-sensitive current, and its current-voltage relationship was similar to that for uninjected oocytes. The reversal potential of the membrane current was studied with [K+]0 of 1-77 mM. For [K+]0 greater than 20 mM, the reversal potential changed with a slope of 63 mV (+/- 2 mV S.E.M.) per 10-fold change in [K+]0. The conductance was induced half-maximally at 17 mV (+/- 0.9 mV S.E.M.). The depolarization required for an e-fold increase in conductance was 13 mV (+/- 0.6 mV S.E.M.). From these results, we conclude that the injection of total RNA from carp retinas induces the formation of a membrane K+ channel in Xenopus oocytes. The channel formed has many of the properties reported for the maintained outward current of goldfish horizontal and bipolar cells.

Animals↗
PubMed1991

A randomized trial of chemotherapy followed by pelvic radiation therapy in stage IIIB carcinoma of the cervix.

Because of the poor results in stage III B carcinoma of the cervix with standard treatment using radiotherapy alone, we designed a randomized trial to determine whether administration of chemotherapy before pelvic irradiation would improve survival. Between May 1984 and August 1986, 107 patients with previously untreated squamous cell carcinoma were randomly assigned, after stratification by age (less than 50 v greater than 50 years), extent of parametrial involvement (unilateral v bilateral), and lymphangiographic findings (negative v positive) to pelvic radiotherapy (RT; arm A) or three cycles of chemotherapy (CT; bleomycin, vincristine, mitomycin, and cisplatin [BOMP]), followed by the same radiotherapy regimen (CT + RT; arm B). The groups were balanced by age, performance status, extent of parametrial involvement, bulkiness of cervical disease, nodal involvement, and presence of hydronephrosis. Minimal follow-up is 34 months. A complete local response was observed in 32.5% of the patients in arm A and in 47% of the patients in arm B (P = .19). Overall 5-year survival rates were 39% for the RT arm and 23% for the CT + RT approach (P = .02). Toxicity was severe in arm B and included fatal pulmonary toxicity in four patients. Locoregional and distant failures were similar in both groups. We conclude that, despite a satisfactory response rate, neoadjuvant BOMP chemotherapy adversely affects survival in stage III B cervical cancer and is associated with unacceptable toxicity.

Aged↗
PubMed1990

The binding of somatostatin to the mouse retina is altered by the pearl mutation.

Pearl mutants have a night-blind phenotype and abnormal optokinetic nystagmus. Preliminary results from another study showed that the light responses of retinal ganglion cells of pearl mutant mice were affected by bathing the isolated retina with low (less than 1 nM) concentrations of either somatostatin-14 or -28, whereas the responses in wild-type retinas were affected only by somatostatin-28. In order to test the possibility that these physiological differences resulted from alterations in receptor affinity, we studied the binding of 125I-[Tyr11]-somatostatin-14 and 125I-[Leu8,D-Trp22,Tyr25]-somatostatin-28 to frozen, unfixed sections of eyes of wild-type (C57BL/6J +/+) and congenic pearl mutant (C57BL/6J-pin pe(pin)/pe(pin)) mice. As found previously for wild-type mice, specific binding occurred in 3 maxima in pearl mutants: a broad band extending from the retinal ganglion cell to the inner nuclear layer, a narrow and inconstant band over the outer plexiform layer, and a band over the pigment epithelium and choroid. We quantified the label over the inner plexiform layer and found evidence for a single saturable site in both genotypes. However, several results indicate that somatostatin-14 binds more avidly to pearl mutant retinas than to wild-type retinas. In saturation binding studies, Kd for 125I-[Tyr11]-somatostatin-14 was 600 pM in pearl mutants vs 1.5 nM in wild-type; whereas, for 125I-[Leu8,D-Trp22,Tyr25]-somatostatin-28, Kd was nearly equal in the two genotypes (500 and 625 pM, respectively). Bmax was nearly equal for both ligands in both genotypes (63-69 fmol/mg protein).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

The pearl mutation accelerates the schedule of natural cell death in the early postnatal retina.

The time of maximal occurrence of pyknotic nuclei in the retinal ganglion cell layer of postnatal pearl mutant mice is earlier than that in normal mice (Linden and Pinto 1985). Both ganglion and displaced amacrine cells and glia populate the ganglion cell layer. Thus, in order to show that ganglion cells themselves are affected, we counted the numbers of surviving axons in the optic nerve of postnatal day (PND) 0, 4, 12 and adult mice. On PND 0, pearl mutant mice had 139,000 +/- 2800 (SEM) optic axons, about 8% more than wild-type mice (128,000 +/- 1,700; p = 0.031) but on PND 4, pearl mutants had 24% fewer axons than wild-type mice (96,000 +/- 3700 and 119,000 +/- 4600, respectively; p = 0.008). Thus, pearl mutants lose nearly five times as many retinal ganglion cells as wild-type mice in the interval from PND 0 to 4. The number of axons present in adult mice was nearly equal (56,700 +/- 3200 for wild-type and 52,500 +/- 2700 for pearl mutants p = 0.37). We searched for evidence for changes in the schedule of cell death among other neurons of the retina by counting the number of pyknotic nuclei in the various retinal layers. On PND 4, pearl mutant mice had more pyknotic nuclei in the neuroblastic layer than wild-type mice (5000 +/- 400 and 3900 +/- 300, respectively; p less than 0.05). The time-course of the appearance of pyknotic nuclei in the outer nuclear layer differed for the two genotypes (ANOVA, F = 12.5, p less than 0.001). The most striking difference was a greater number of pyknotic nuclei on PND 20 for the pearl mutants (1300) than for wild-type (480; p = 0.002). However, the total number of photoreceptors in adults did not differ between the two genotypes (3.6 x 10(6) +/- 2.4 x 10(5) for wild-type and 3.7 x 10(6) +/- 3.3 x 10(5) for pearl; p greater than 0.8). These results, taken together, show that natural cell death occurs at an earlier time for retinal ganglion cells of pearl mutants, but that the total number of retinal neurons surviving to adulthood is not affected appreciably by the mutation.

Animals↗
PubMed1989

Localization and characterization of somatostatin binding sites in the mouse retina.

We studied the binding of [125I]Tyr11-somatostatin-14 and [125I]Leu8,D-Trp22,Tyr25-somatostatin-28 to frozen, unfixed sections of C57BL/6J mouse eyes with autoradiography. Specific binding of both ligands occurred in 3 maxima, a broad band extending from the retinal ganglion cell to the inner nuclear layers, a narrow and inconstant band over the outer plexiform layer, and a band over the retinal pigment epithelium and choroid. We quantified the label over the inner plexiform layer and found evidence for a single, saturable binding site after Scatchard analysis of saturation binding data. With [125I]Tyr11-somatostatin-14 the dissociation constant (Kd) was 1.48 nM and the total number of binding sites (Bmax) was 68 fmol/mg protein; in competition experiments the inhibitory binding constant (Ki) was 900 pM for somatostatin-14 and 350 pM for somatostatin-28. With [125I]Leu8,D-Trp22,Tyr25-somatostatin-28, Kd was 625 pM and Bmax was 69 fmol/mg protein; in competition experiments Ki was 4.58 nM for somatostatin-14 and 710 pM for somatostatin-28. These results demonstrate the existence of somatostatin receptors in the inner plexiform layer of the retina that appear to have greater specificity for somatostatin-28 than for somatostatin-14.

Animals↗
PubMed1989

Transient calcium current of retinal bipolar cells of the mouse.

1. Isolated bipolar cells were obtained by enzymic (papain) dissociation of the adult mouse retina. The membrane voltage was clamped and the membrane currents were measured by the whole-cell version of the patch-clamp technique. Isolated bipolar cells and horizontal cells of the goldfish retina were also studied for comparison. 2. Hyperpolarization from the holding voltage, Vh, of -46 mV evoked a slowly activating, Cs+-sensitive, inward current (probably an h-current), and depolarization evoked a TEA- and Cs+-sensitive outward current (probably a combination of K+ currents). 3. Depolarization from a more negative Vh (e.g. -96 mV) evoked a transient inward current that had maximal amplitude between -40 and -20 mV. This current was identified as a Ca2+ current (ICa): its amplitude was increased with elevated [Ca2+]o and was decreased with reduced [Ca2+]o, and it was blocked by 4 mM-Co2+, but not by 5 microM-TTX. 4. Both the perikaryon and the axon terminal generated ICa with similar properties. 5. The plot of Ca2+ conductance (gCa) against membrane voltage (activation curve) was sigmoidal: in 10 mM [Ca2+]o, gCa increased for membrane voltages more positive than -65 mV, was half-maximal at about -25 mV, and reached saturation at about +30 mV. The plot of inactivation of gCa against membrane voltage was also sigmoidal: with 1 s conditioning depolarization in 10 mM [Ca2+]o, gCa decreased for membrane voltages more positive than -80 mV, was half-maximal at about -50 mV, and was fully suppressed for voltages greater than -30 mV. 6. ICa in the mouse bipolar cells was insensitive to 50 microM-Cd2+, 10 microM-nifedipine and 10 microM-Bay K 8644. In contrast, the calcium currents of bipolar and horizontal cells of the goldfish retina were markedly suppressed by 50 microM-Cd2+ and 10 microM-nifedipine, and were augmented several fold by 10 microM-Bay K 8644. The calcium currents of goldfish bipolar and horizontal cells were sustained, and were activated in a more positive range of potentials than the ICa of mouse bipolar cells. 7. The voltage range at which the ICa of mouse bipolar cells is activated includes the presumed range of membrane potentials spanned during light-evoked responses; thus, this current may participate in synaptic transmission. The transient character of ICa may also help to shape transient responses of ganglion cells.

Animals↗
PubMed1987

Retinopretectal and accessory optic projections of normal mice and the OKN-defective mutant mice beige, beige-J, and pearl.

Retinal projections to the pretectal and terminal accessory optic nuclei were studied in normal wild-type mice and mutant mice with abnormal optokinetic nystagmus (OKN, Mangini, Vanable, Williams, and Pinto: J. Comp. Neurol. 241:191-209, '85). The mutants used were pearl, which exhibits an inverted OKN in response to stimulation of only the temporal retina, and beige and beige-J, which show inverted OKN in response to stimulation of only the temporal retina and, in addition, exhibit eye movements with a vertical component in response to horizontally moving, full-field stimuli. These projections were studied following intraocular injections of 3H-proline or horseradish peroxidase (HRP) with, respectively, light microscopic autoradiography or HRP histochemistry. In wild-type mice, strong contralateral retinal projections covered the entire nucleus of the optic tract, the anterior and posterior divisions of the olivary pretectal nucleus, and the posterior pretectal nucleus. Similar heavy contralateral projections were distributed over the dorsal and medial terminal nuclei of the accessory optic system. Also, terminals sparsely covered the entire neuropil of the contralateral lateral terminal nucleus in some but not all wild-type mice. The most prominent accessory optic input was to the medial terminal nucleus and was provided by the inferior fasciculus of the accessory optic tract. A typical mammalian superior fasciculus of the accessory optic system with anterior, middle, and posterior components was present. Ipsilateral label was found in anterior and posterior olivary pretectal nuclei in all of the wild-type animals, but was found inconsistently in the ipsilateral terminal accessory optic nuclei. The pattern of contralateral retinal projection to the nucleus of the optic tract and posterior pretectal nucleus in mutants was indistinguishable from that seen in the normal wild-type mice. However, retinal inputs to the ipsilateral anterior and posterior olivary pretectal nuclei were significantly reduced in pearl mutants and were exceedingly sparse in the beige and beige-J mutant mice, while the contralateral inputs to these nuclei were increased in a complementary fashion in the mutants. The labeling of the accessory optic input to the contralateral dorsal terminal nucleus appeared to be substantially reduced in all of the mutant mice. The size of the principal accessory optic fascicle, the inferior fasciculus, was significantly smaller in beige, beige-J, and pearl mice; this reduction was greater in the beige and beige-J than in the pearl mice.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Response properties of horizontal cells in the isolated retina of wild-type and pearl mutant mice.

Intracellular recordings were made from axon bearing horizontal cells in isolated retinas (with retinal pigment epithelium removed) of normal and pearl mutant mice superfused with mammalian Ringer's solution. Cells were injected with Lucifer yellow and identified by their morphology and their response wave-forms. On impalement, we measured a dark, resting voltage of 25-35 mV. All cells had similar spectral sensitivities that were consistent with the CIE scotopic relative spectral luminosity function. For stimuli of high irradiance, two types of responses could be distinguished, based on their waveform at stimulus offset. One consisted of a rapid and wavelength-dependent repolarization followed by a small, slow hyperpolarization. The other consisted of a large, long-lived, and wavelength-independent after-hyperpolarization. The former were recorded from the somatic end and the latter from the axon terminal arborization. The spatial distribution of sensitivity was measured in over 100 locations within the receptive field using small stimuli. The area within which sensitivity of the soma was within 0.1 log unit of the maximal sensitivity was larger than that of the soma dendritic field, but the sizes were nearly equal for the terminal arborization. No secondary maximum of sensitivity was noted over the dendritic field of the unimpaled part of the cell. For the terminal arborization, the half-saturating irradiance for diffuse 502 nm stimuli was about 180 photons micron-2 sec-1, about one-tenth that for the soma. These values are in good agreement with those for cat and rabbit.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

The optokinetic nystagmus and ocular pigmentation of hypopigmented mouse mutants.

We tested the optokinetic nystagmus (OKN) reflex of various hypopigmented mutant mice and ultrastructurally examined the pigmentation of various ocular structures in these mutants. Using electron microscopy we examined the pigmentation of the choroid and retinal pigment epithelium (RPE) and measured the numerical density, volume density, and distribution of RPE melanosomes of mice with the following phenotypes: (1) wild type, (2) mutants that have abnormal or no OKN in response to horizontally moving, full-field stimulation, and (3) other mutants that have normal OKN but reduced choroidal pigmentation. We also measured the OKN of all these mice in response to horizontally moving stimuli that were restricted to the nasal or to the temporal retina. We found that in the mutants with normal OKN the numerical density of melanosomes in the RPE was within the range found for wild type, while the numerical density was reduced for the mutants with abnormal OKN. For one mutant with normal RPE pigmentation and normal OKN, the choroidal pigmentation was nearly absent. For the genotypes with abnormal OKN the volume density of the RPE melanosomes and percent apical melanosomes were sometimes greater and sometimes less than normal. The OKN patterns of these mice fell into the following categories: (1) wild type; (2) field-restriction dependent OKN with small following movements but no OKN in response to full-field stimulation, normal OKN in response to stimulation of the nasal retina, and OKN of reversed direction in response to stimulation of the temporal retina; (3) oblique with slow oblique following movements and reduced numbers of OKNs with oblique quick phases in response to horizontally moving, full-field stimulation, nearly normal OKN in response to stimulation of the nasal retina, and OKN of reversed direction in response to stimulation of the temporal retina. The horizontal component of the oblique response to full-field stimulation was in the same direction for the two eyes, but the vertical component was in the opposite direction. (4) Slow, small amplitude, with no or very small following movements in response to full-field stimulation, following movements in response to stimulation of the nasal retina and reversed "following" movements in response to stimulation of the temporal retina but few or no quick phases of the OKN for any stimulus condition. These results show that a variety of abnormalities of the OKN occur for hypopigmentation mutants of the mouse.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Developmental genetics of the retina: evidence that the pearl mutation in the mouse affects the time course of natural cell death in the ganglion cell layer.

The time course of natural cell death was studied postnatally in the ganglion cell and inner plexiform layers of the retina in the developing mouse. We examined congenic wild-type, albino and pearl mutants from birth to 12 days of age. In both wild-type and albino mice, natural cell death proceeded with an increasing rate from birth to a peak 6 days after birth, and with a decreasing rate thereafter. In contrast, cell death in pearl mutants proceeded with essentially a decreasing rate postnatally. The populations of neurones and glial cells in the ganglion cell and inner plexiform layers of the retina were also determined in adult mice. It was shown that pearl mutants had a slightly smaller number of cells in those layers than both wildtype and albino mice, and that the difference was probably due entirely to the numbers of neurones. We conclude that the pearl mutation in the mouse affects the timing of developmental cell death, but the effect is not directly related to the amount of pigment in the eye.

Animals↗
PubMed1985

Synaptic lamellae of the photoreceptors of pearl and wild-type mice.

The retina of the pearl mutant mouse, C57BL/6J pe/pe, exhibits reduced light sensitivity in the dark-adapted condition (Balkema and Pinto, J Neurophysiol 48:968, 1982). The authors searched for an anatomic correlate in the retina which could relate to the functional deficit. Electron microscopic mosaics of the outer plexiform layer of light- and dark-adapted pearl and wild-type mice were analyzed. The numerical density and length of the photoreceptor synaptic lamellae showed these parameters to be indistinguishable in wild-type and pearl retinas under conditions of both light- and dark-adaptation. Light-adapted pearl retinas exhibited some rod spherules that contained structurally modified synaptic lamellae with bulbous thickenings and adjacent electron-dense bodies. These lamellar modifications were neither apparent in the light-adapted, wild-type retinas, nor in the dark-adapted retinas of either genotype. Pronase application to ultrathin sections hydrolyzed synaptic lamellae, bulbous thickenings and electron dense bodies.

Animals↗
PubMed1985

The retinal pigment epithelium of wild type (C57BL/6J +/+) and pearl mutant (C57BL/6J pe/pe) mice.

The retinal pigment epithelium (RPE) lying along the vertical meridian of the eyes of wild-type (+/+) and pearl mutant (pe/pe) mice was examined with electron microscopy and microspectrophotometry in order to compare differences in melanosome location, size, numerical density, volume density, and melanin concentration. In +/+ mice the fraction of melanosomes that lie in the apical processes was greater in the superior than in the inferior retina. Also, the numerical density and volume density of soma melanosomes were lower in the superior retina. The soma melanosomes were also located closer to the basal membrane and had a larger average diameter in the inferior retina. No significant differences in melanosome location were observed between light-adapted and dark-adapted retinas. In pe/pe mice the fraction of melanosomes in the apical processes was very low in both inferior and superior retinas. The numerical density and the volume density of soma melanosomes of pe/pe were significantly less than those of +/+. The soma melanosomes of pe/pe mice lie closer to the basal membrane than those of +/+, and they had a larger mean diameter than those of +/+. Electron micrographs depicted some melanosomes of pe/pe with irregular profiles and abnormal melanin deposition at their periphery. Microspectrophotometric measurements of individual melanosomes in semithin sections showed that maximal specific absorption and lambda max were nearly equal for both genotypes and both superior/inferior locations. These findings show that intramelanosomal melanin concentrations is normal for pe/pe. The basal membrane of the RPE of pe/pe was infolded over only 80% of the area covered by the basal surface, whereas the basal membrane in +/+ was infolded over more than 98% of the area covered. The boundary density of RPE basal infoldings was also lower in pe/pe than in +/+. Furthermore, some areas of the basal lamina of pe/pe RPE had a periodic, rather than an amorphous, structure. These findings suggest that the reduced retinal sensitivity found in intact pe/pe animals, but not in superfused, isolated pe/pe retinas, may result from impaired transport of a diffusible substance by the basal membrane of the RPE.

Animals↗