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PubMed2002

Prescribing second-generation antipsychotics and the evolving standard of care in Italy.

The present study was carried out to investigate the routine use of second-generation antipsychotic drugs in the Italian psychiatric care system. Seven outpatient psychiatric services enrolled a consecutive case series of patients who were being treated, or had started treatment, with clozapine, olanzapine, risperidone, or quetiapine. Information on sociodemographic and clinical variables, current psychotropic drug use, side-effects and past use of typical drugs was collected. In addition, patient symptoms and functional status were evaluated by the Health of the Nation Outcome Scale. Patients receiving off-label prescribing of second-generation antipsychotics were identified. A total of 209 patients were collected. In comparison with patients receiving other second-generation antipsychotics, living in residential facilities, unemployment, long psychiatric histories, and problems with activities of daily living and living conditions were more common in clozapine-treated patients. Nearly 80 % of patients receiving clozapine had schizophrenia compared to less than 50 % of those receiving other second-generation antipsychotics. Overall, 109 patients (52 %) received off-label prescriptions of second-generation antipsychotic drugs. This survey indicates that clozapine was mostly reserved for severe cases and poor responders; the high rate of off-label prescriptions highlights the gap existing between recommendations derived from randomised clinical trials and the current use of drugs.

Adolescent↗
PubMed2003

Diffusion of new generation antidepressant treatment among elderly diagnosed with depression.

RESEARCH OBJECTIVE: This study analyzes the prevalence of new generation antidepressant treatment including selective serotonin reuptake inhibitor (SSRI) use from 1992 to 1997 among the elderly diagnosed with depression, using a large, nationally representative survey of Medicare beneficiaries. Relationships between use of new generation antidepressant treatment and socioeconomic characteristics, physical comorbidity, insurance coverage, and care sector (mental health specialty vs. general health services) are explored. RESEARCH DESIGN: Merged survey data, Medicare claims, and detailed self-reports from the Medicare Current Beneficiary Survey were used to explore use of new generation antidepressant treatment.SUBJECTS Medicare beneficiaries aged 65 and older living in the community, enrolled in fee-for-service Medicare throughout the year and diagnosed with depression. RESULTS: In 1997, among an estimated 1.1 million community dwelling older adults with diagnosis of depression in health care claims, nearly two thirds received antidepressant treatments. Among those diagnosed with depression and treated with antidepressants, the use of new generation antidepressants increased from 35% in 1992 to 77% in 1997. The rates of use increased among all subgroups examined. In the early years after the introduction of these new antidepressant medications (1992-1994), there were socioeconomic disparities in use of these medications, with less use by less educated and poor patients. However, these differences abated over time. CONCLUSIONS: An increasing proportion of elderly treated for depression with antidepressants received the new generation antidepressants. The diffusion of these new medications lagged for those with low socioeconomic status defined by education and income. This diffusion process conforms to a general model of diffusion in which during the initial years following introduction of a new treatment, especially one which is costly, early adopters of the treatment are likely to disproportionately represent those of higher socioeconomic status.

Age Factors↗
PubMed2026

PD GENEration: An International Parkinson's Disease Genetic Research Study.

BACKGROUND: PD GENEration (NCT04057794, NCT04994015), sponsored by the Parkinson's Foundation in partnership with Aligning Science Across Parkinson's (ASAP) through the Global Parkinson's Genetics Program (GP2), is an international, observational, clinical research study that offers genetic testing and counseling to people living with Parkinson's disease (PwP) at no financial cost. PD GENEration has aimed to empower PwP and their clinicians with knowledge of their genetic status, to accelerate recruitment into precision medicine trials, and to advance research through data sharing. Since its launch in 2019, the study has expanded to enroll over 32,000 PwP (as of March 31, 2026), from 10 countries across North, Central, and South America, the Caribbean, and Israel. METHODS: Over the course of 6 years, PD GENEration has evolved to accommodate the growing scientific and research needs of the Parkinson's community while also increasing the ability to return genetic test results to PwP at a greater scale. Participants with a diagnosis of Parkinson's disease (PD) may enroll in-person or virtually where informed consent and blood sample collection can occur. Samples are analyzed at a College of American Pathologists/Clinical Laboratory Improvement Amendments (CAP/CLIA)-certified laboratory using whole genome sequencing, with variants curated for a primary panel of seven PD-associated genes. Results are disclosed during a genetic counseling visit, where further testing is offered for two optional additional gene panels. Those who consent undergo analysis of additional genes, and results are returned during a genetic counseling visit for those that test positive for a variant. In addition to returning genetic results to PwP, a central pillar of the study design has been the open sharing of genomic data to advance discovery in PD research in partnership with ASAP and GP2. DISCUSSION: PD GENEration applies a flexible framework, allowing for country specific considerations and the integration of multiple site models, evolving based on participant needs and the prioritization of equity and accessibility. We summarize PD GENEration's implementation and scaling, highlight key accomplishments and lessons learned, and provide guidance for those interested in implementing large-scale clinical genetic testing studies across other diseases and therapeutic domains.

Parkinson’s disease↗
PubMed1988

An improved tungsten-178/tantalum-178 generator system for high volume clinical applications.

Clinical utilization of the multiwire gamma camera (MWGC) requires low-energy radionuclides. The short-lived (9.3 min) tantalum-178 (178Ta) is ideally suited for the MWGC and can be produced from long-lived (21.7 day) tungsten-178 (178W) by a previously reported 178W/178Ta generator. This generator, however, is limited by sharp increase in breakthrough after elution of only 30-60 column-volumes. To optimize the 178W/178Ta generator for clinical use, varying eluant acid concentrations were evaluated. A reduced (from 0.1 to 0.03N) HCI concentration in the eluant, coupled with low operating temperatures (3 to 5 degrees C) allowed high (40 to 60%) 178Ta yield. Minimal 178W breakthrough (less than .01%) resulted, even after elution of more than 200 column-volumes. Each of six tested generators provided sterile, high activity (up to 100 mCi) 178Ta elutions for more than 30 days. Radiation dosimetry was estimated utilizing both human and animal biodistribution data. The whole body (critical organ) dose in adults and neonates were 1/20 (1/21) and 1/19 (1/50) respectively relative to that of technetium-99m (99mTc) as sodium pertechnetate. The optimized 178W/178Ta generator provides a commercially practical, safe source of low-energy radioisotope for the MWGC with substantial dosimetry advantages over 99mTc.

Animals↗
PubMed1987

An osmium-191/iridium-191m radionuclide generator using an oxalato osmate parent complex.

A new osmium-191/iridium-191m (191Os/191mIr) radionuclide generator has been developed that offers high 191mIr yield (greater than 20%/ml) and low 191Os breakthrough (less than 5 X 10(-4)%/ml) when eluted with a solution of 0.001 M oxalic acid and 0.9% (normal) saline. This is the first 191Os/191mIr generator that combines the advantages of high 191mIr yield, extremely low 191Os breakthrough, and an eluate that does not require buffering prior to injection. These improvements in performance were accomplished through use of the chelate transdioxobisoxalatoosmate(VI) as the parent complex on the generator. The clinical result of the combination of higher yield and lower breakthrough is a 100-fold decrease in the estimated patient radiation dose compared with the same study performed with technetium-99m (99mTc), and the injectable eluate makes the generator easier to use. Acute and subacute toxicity studies performed on this generator eluate have shown no adverse effects attributable to the eluate.

Iridium↗
PubMed1986

A new osmium-191/iridium-191m radionuclide generator system using activated carbon.

A new osmium-191/iridium-191m (191Os/191mIr) radionuclide generator system has been developed based on the absorption of K2OsCl6 (Os-IV) on 140-230 mesh heat-treated activated carbon. The generator is eluted with pH 2 saline solution containing 0.25 g/l Kl to give 191mIr in good yield. The generator eluent is neutralized to physiologic pH and isotonicity with Tris buffer immediately prior to i.v. injection. No scavenger column is required. As an example, elution of the prototype generator with a 2-ml bolus results in elution of 191mIr in approximately 18% yield with an 191Os breakthrough of only 2 X 10(-4)%/bolus. The prototype generator has consistent performance over a 2-wk period with no change in 191mIr yield or 191Os breakthrough. Loading of up to 1.5 Ci of 191Os results in no observed radiolysis. Continuous elution of this system is also possible with a mean 191mIr yield of 3.7%/ml and a mean 191Os breakthrough of 2 X 10(-5)%/ml at a flow rate of 12 ml/min. This new system represents a readily available source of 191mIr for radioangiography. Adsorbed radiation dose calculations indicate a total-body dose of only 3.9 mrad for a 100 mCi injected bolus.

Adsorption↗
PubMed1980

A new osmium-191 leads to iridium-191m generator.

A new osmium-191 leads to iridium-191m generator suitable for first-pass radionuclide angiocardiography has been developed. This generator system allows repeated elutions of 4.96-sec iridium-191m from its 15.4-day Os- 191 parent. The Os-191 is loaded on an anion-exchange column (AGMP-1) and Ir- 191m eluted with 0.9% NaCl at pH 1. Each elution (0.6 to 1 ml) of the generator yields about 7 to 10% Ir-191m and gives 0.003-0.008% of Os-191 breakthrough. Toxicity studies of the generator eluate carried out in animals support the safety of using iridium-191m in humans. The long shelf-life of the generator (approximately equal to 2 wk) will allow medical centers to use Ir- 191m for routine clinical diagnosis. Iridium-191m obtained by this method should find additional useful applications in nuclear medicine.

Animals↗
PubMed2005

Injury risk to restrained children exposed to deployed first- and second-generation air bags in frontal crashes.

OBJECTIVE: To estimate the risk of serious nonfatal injuries in frontal crashes among belted children seated in the right front seat of vehicles in which second-generation passenger air bags deployed compared with that of belted children seated in the right front seat of vehicles in which first-generation passenger air bags deployed. DESIGN AND SETTING: We enrolled a probability sample of 1781 seat belt-restrained occupants aged 3 through 15 years seated in the right front seat, exposed to deployed passenger air bags in frontal crashes involving insured vehicles in 3 large US regions, between December 1, 1998, and November 30, 2002. A telephone interview was conducted with the driver of the vehicle using a previously validated instrument. The study sample was weighted according to each subject's probability of selection, with analyses conducted on the weighted sample. Main Outcome Measure Risk of serious injury (Abbreviated Injury Scale score of > or =2 injuries and facial lacerations). RESULTS: The risk of serious injury for restrained children in the right front seat exposed to deployed second-generation passenger air bags was 9.9%, compared with 14.9% for similar children exposed to deployed first-generation passenger air bags (adjusted odds ratio, 0.59; 95% confidence interval, 0.36-0.97). CONCLUSION: This study provides evidence based on field data that the risk of injury to children exposed to deploying second-generation passenger air bags is reduced compared with earlier designs.

Accidents, Traffic↗
PubMed1997

Five generations of selective breeding for ultrasonic vocalization (USV) responses in N:NIH strain rats.

This article reports on early results from an ongoing selective breeding study in which rats were selected for different rates of ultrasonic vocalization (USV) in response to isolation. Using the N:NIH strain, all litters were screened at 10 (+/- 1) days of age in a 2-min isolation test, and those males and females with the highest (or lowest) rates in each litter were selected for later breeding with like breeders from unrelated litters. A Random line (unselected control) was also bred. In the first selected generation (S1), the Low line diverged from Random line controls, and has maintained significantly lower rates over all generations since. In the S3 generation, the High line diverged significantly from Random line controls, and has shown significantly higher USV rates in each succeeding generation. No line differences were found in other behaviors measured in isolation. Data from a small sample of S5 pups tested at postnatal Days 3, 10, 14, and 18 days showed that individual pups' rates of USV from Day 10 predicted those at Day 14, consistent with findings from an unselected generation. Ambient temperature, modulated by body weight, controlled USV at Day 3, whereas at Days 10 and 14 line accounted for most of the variance in USV. This is the first instance of laboratory selection occurring on the basis of an infantile trait.

Age Factors↗
PubMed1999

Synthesis and relaxometry of high-generation (G = 5, 7, 9, and 10) PAMAM dendrimer-DOTA-gadolinium chelates.

A series of high-generation (G) ethylenediamine-core polyamidoamine (PAMAM) dendrimers corresponding to G = 5, 7, 9, and 10 were conjugated with the bifunctional chelate 2-(4-isothiocyanatobenzyl)- 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetate (p-SCN-Bz-DOTA). Gadolinium (III) ion was added to the macromolecules, and the 1/T1 and 1/T2 NMRD profiles were measured at 3 degrees, 23 degrees, and 37 degrees C. The synthesis resulted in preparations that ranged from an average of 127 chelates and 96 Gd3+ ions per G = 5 dendrimer to an average of 3727 chelates and 1860 Gd3+ ions per G = 10 dendrimer. At 20 MHz and 23 degrees C, the 1/T1 ion relaxivity increased from 30 mM(-1) s(-1) for the G = 5 to 35 mM(-1) s(-1) for the G = 7 PAMAM dendrimer-DOTA-Gd, reaching a plateau at 36 mM(-1) s(-1) for the G = 9 and G = 10 dendrimers. A similar plateau was observed for 1/T2 with values of 36 mM(-1) s(-1) for G = 5, 42 mM(-1) s(-1) for G = 7, and 45 mM(-1) s(-1) for the G = 9 and G = 10 dendrimers. This "saturation" of ion relaxivity for high-generation dendrimers occurred over the entire frequency range studied. The 1/T1 and 1/T2 relaxivities decreased as the temperature decreased for each generation of dendrimer studied, implying that slow water exchange of bound water molecules with the bulk solvent limits the relaxivity. In such circumstances, increases in the rotational correlation time of the macromolecules associated with higher generations of dendrimer does not result in significant increases in the ion relaxivity. Although the ion relaxivity does not increase, the total molecular relaxivities increased from 2880 mM(-1) s(-1) to 66960 mM(-1) s(-1) for the G = 5 to the G = 10 dendrimer. The current findings are relevant for the design of high-generation dendrimer-based receptor agents.

Contrast Media↗
PubMed2003

New generation antipsychotics for first episode schizophrenia.

BACKGROUND: The new generation antipsychotics are associated with a lower risk of adverse effects compared with drugs such as haloperidol. Many treatment guidelines recommend the use of new generation ('atypical') antipsychotic drugs for people with a first episode of schizophrenia. OBJECTIVES: To examine the effects of the new generation antipsychotics for people with a first episode of schizophrenia or schizophrenia-like psychoses. SEARCH STRATEGY: The reviewers searched the Cochrane Schizophrenia Group's register (March 2002) and the included and excluded studies tables of relevant Cochrane reviews, references of all relevant studies, contacted industry and authors of relevant studies to identify further trials. SELECTION CRITERIA: Randomised clinical trials comparing new generation antipsychotics (amisulpride, clozapine, olanzapine, quetiapine, risperidone, sulpiride, ziprasidone, zotepine) with conventional antipsychotics for people with a first episode of schizophrenia or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: Citations and, where possible, abstracts were independently inspected by three reviewers, papers ordered, re-inspected and quality assessed. We independently extracted data but excluded them if loss to follow up was greater than 50%. For homogeneous dichotomous data, we calculated the relative risk (RR), the 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT), on an intention-to-treat basis. For continuous data, reviewers calculated weighted mean differences (WMD). MAIN RESULTS: We include two short-term studies (total n=266), one of which was a report of a sub-group of a larger study. One compared risperidone with an average of 6 mg/day haloperidol and the other olanzapine with an average of 11 mg/day haloperidol. Compared with olanzapine, significantly more people receiving haloperidol left the study early (n=83, 1 RCT, RR 0.43 CI 0.3 to 0.7, NNH 3 CI 2 to 8). This was not so for the risperidone versus haloperidol comparison (n=183, 1 RCT, RR=0.7 CI 0.4 to 1.1). In terms of global effects, studies reported no differences between risperidone and haloperidol (n=183, RR not much improved 1.0 CI 0.6 to 1.5), and olanzapine and the same control (n=83, RR needing at least one dose of benzodiazepine 0.8 CI 0.5 to 1.1). More people allocated to olanzapine had clinically significant improvement in mental state compared with those given haloperidol (n=83, RR no 'clinically significant improvement' 0.45 CI 0.3 to 0.7, NNH 3 CI 2 to 6). In the risperidone study, however, no such difference was apparent (n=183, RR 'no clinically significant improvement in mental state' 0.85 CI 0.6 to 1.2). Significantly more people given haloperidol (4-16mg) experienced at least one adverse event when compared with risperidone (4-16mg) (n=183, RR 0.9 CI 0.8 to 0.98, NNH 8 CI 4 to 50). Use of anticholinergic medication for extrapyramidal adverse events was less prevalent for people allocated either olanzapine (n=83, RR 0.3 CI 0.2 to 0.7, NNH 4 CI 2 to 14) or risperidone (n=183, RR 0.7 CI 0.5 to 0.9, NNH 4 CI 3 to 9) compared with those given haloperidol. There are no data at all on outcomes such as compliance, cost, social and cognitive functioning, relapse, rehospitalisation, or quality of life. There are no medium to long-term data. Eight ongoing studies may provide more information. REVIEWER'S CONCLUSIONS: The results of this review are inconclusive. Whether the use of new generation antipsychotics really makes the treatment less off putting and enhances long-term compliance is unclear. Pragmatic, well-designed and reported long-term trials would be useful to answer this question.

Antipsychotic Agents↗
PubMed2002

The IL-10-producing competence of Th2 cells generated in vitro is IL-4 dependent.

Previous studies have suggested that activation of CD4+ T cells in the presence of IL-10 results in the generation of a population of T cells, T regulatory 1 (Tr1) cells, that primarily produce IL-10 and TGF-beta, but not IL-4. The relationship between Tr1 cells and conventional Th2 cells remains unclear. We were not successful in our attempts to generate significant numbers of antigen-specific T cells that secreted IL-10, but not IL-4, by culture in the presence of IL-10. The small numbers of cells that produced IL-10 only were completely dependent on the presence of IL-4 for their generation. In a polyclonal model, the development of IL-10 only producers was completely dependent on the presence of signal transducer and activator of transcription 6. Studies with myelin basic protein-specific T cells derived from an IL-4-deficient mouse confirmed the absolute requirement for IL-4 for the generation of IL-10 producers under all culture conditions. These IL-10-producing Th2 cells failed to inhibit EAE in an adoptive transfer model and were pathogenic when transferred to immunodeficient mice. Collectively, our results raise doubts about the existence of a unique population of CD4+ regulatory T cells that can be generated by activation in the presence of IL-10.

Animals↗
PubMed2001

Novel fragments of the Sjögren's syndrome autoantigens alpha-fodrin and type 3 muscarinic acetylcholine receptor generated during cytotoxic lymphocyte granule-induced cell death.

OBJECTIVE: To determine whether the Sjögren's syndrome autoantigens alpha-fodrin and the type 3 muscarinic acetylcholine receptor (M3R) are cleaved during cytotoxic lymphocyte granule-induced death, to yield novel fragments. METHODS: Primary salivary gland epithelial cells, human salivary gland cells, and HeLa cells were incubated with granule contents. The susceptibility to cleavage and the generation of novel fragments of Sjögren's syndrome autoantigens in this form of apoptosis was assessed by immunoblotting. Cleavage of M3R was further characterized by assays performed on the M3R molecule generated by in vitro translation. RESULTS: This study demonstrated that alpha-fodrin was uniquely cleaved during cytotoxic lymphocyte granule-induced cell death, generating a 155-kd fragment distinct from those generated by caspase 3 in other forms of apoptosis. The study also demonstrates that M3R (which is restricted in expression to the peripheral autonomic organs) was efficiently cleaved by granzyme B (but not by caspases) at several sites, both in vitro and in intact cells. This is the first description of cleavage of a transmembrane autoantigen by granzyme B. CONCLUSION: The observation that both ubiquitously expressed autoantigens (e.g., alpha-fodrin, La, and nuclear mitotic apparatus protein) and tissue-restricted autoantigens (e.g., M3R) targeted in Sjögren's syndrome are specifically cleaved by granzyme B, generating unique fragments, strongly suggests that a common biochemical event (novel autoantigen cleavage during granule-induced epithelial cell death) is responsible for selecting this apparently unconnected group of molecules for a high-titer autoantibody response. The data focus attention on the role of cytotoxic lymphocytes in the initiation and propagation of Sjögren's syndrome.

Animals↗
PubMed1981

Evidence for the generation of hydroxyl radical during arachidonic acid metabolism by human platelets.

Reactive oxygen species, probably hydroxyl radicals (OH.), have been suggested to be generated during arachidonic acid (AA) metabolism and, once released, these species can modify the rate and extent of various reactions involved in AA metabolism. We have studied this phenomenon in washed human platelets. OH. generation was quantitated using 14C-benzoic acid as a specific trap in a continuous ionization chamber system. Resting platelets did not produce any detectable signal, whereas addition of AA resulted in gradual OH. production with peak values detected at approximately 20 min. Similar studies conducted under nitrogen or after boiling the platelets almost abolished OH. generation. Aspirin had no significant effect, whereas 5,8,11,14-eicosatetraynoic acid decreased the signal by greater than 90%, thus suggesting that OH. is produced primarily through the lipoxygenase pathway. Superoxide dismutase (SOD) and catalase had no effect and, as expected, phenol and mannitol decreased OH. production considerably, by greater than 50% and 90%, respectively. Azide and cyanide also reduced the OH. generation by about two thirds. We conclude that OH. is generated during AA metabolism by human platelets. It is primarily produced via the lipoxygenase pathway and may require a heme-dependent peroxidase. This highly reactive oxidant may play an important role in normal and abnormal hemostasis.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1998

The role of third-generation beta-blocking agents in chronic heart failure.

Third-generation beta-blocking agents developed for the hypertension market are proving useful in the treatment of chronic heart failure (HF). These compounds share the ancillary property of vasodilation, which improves acute tolerability by unloading the failing left ventricle at a time when beta-adrenergic withdrawal produces myocardial depression. In the case of carvedilol and bucindolol, this allows for the administration of nonselective beta blockade. Because of blockade of both beta 1 and beta 2 adrenergic receptors as well as other properties, these compounds possess a more comprehensive antiadrenergic profile than second-generation, beta 1-selective compounds. For this and potentially other reasons, third-generation beta-blocking agents have theoretical efficacy advantages that have yet to be demonstrated in large-scale trials. Ongoing trials with either second- or third-generation compounds and one trial directly comparing a compound from each class will provide the answer as to whether third-generation compounds have an advantage in the treatment of chronic HF.

Adrenergic beta-Antagonists↗
PubMed1995

Strikingly different propulsive forces generated by different dynein-deficient mutants in viscous media.

The propulsive force generated by Chlamydomonas mutants deficient in flagellar dynein was estimated from their swimming velocities in viscous media. The force produced by wild-type cells increased by 30-40% when viscosity was raised from 0.9 to 2 cP but decreased as viscosity was further raised above 6 cP. The biphasic dependence of force generation on viscosity was also observed in the mutant ida1, which lacks the I1 component of the inner-arm dynein. The mutant ida4, which lacks the inner-arm I2 component, was extremely susceptible to viscosity and stopped swimming at 6 cP, at which other mutants could swim. In contrast, oda1, which lacks the entire dynein outer arm, produced a fairly constant force of about one-third of the wild-type value, over a viscosity range of 0.9-11 cP. In demembranated and reactivated cell models of the wild type, the propulsive force decreased monotonically as viscosity increased. Thus the increase in force generation at about 2 cP observed in live cells may be caused by some unknown mechanism that is lost in cell models. The cell models of oda1, in contrast, did not show a marked change in force generation with the change in viscosity. These results indicate that the force generation by the outer-arm dynein greatly depends on viscosity or the velocity of movement, whereas the complete set of inner-arm dynein present in the oda1 axoneme produces a fairly constant force at different viscosities. These different properties of inner and outer dynein arms should be important in the mechanism that produces flagellar beating.

Animals↗
PubMed1979

Rods and cones in the mouse retina. II. Autoradiographic analysis of cell generation using tritiated thymidine.

The period of cell genesis of rod and cone photoreceptor cells has been determined in the retinas of C57BL/6J mice. Embryonic mice were exposed to a single dose of 3H-thymidine at embryonic day (E) 10--18 by injecting pregnant mice intraperitoneally. Animals at postnatal ages were injected subcutaneously once between postnatal day (P) 0--10. The eyes were removed at one to three months of age. After fixation, they were embedded in glycol methacrylate, sectioned at 1.5 micrometers and prepared for autoradiographic analysis. All of the cone cells are generated over a relatively short time interval during the fetal period. In the posterior retina, the peak of cone cell genesis occurs at E13-E14, and no cones are generated after E16. The rods, by contrast, are generated later and over a longer time period. They first begin to be generated in the posterior retina on E13, but the peak of cell genesis is not reached until the day of birth, and some rods are generated as late as P5. For both rods and cones the peaks of cell genesis in the peripheral retina occur two to three days later than in the posterior retina. The findings demonstrate that rods and cones are developmentally distinct cell types in the mouse retina.

Animals↗
PubMed1986

Cell generation, death, and retinal growth in the development of the hamster retinal ganglion cell layer.

During the early postnatal period in the hamster, the retinal ganglion cell layer grows, establishes its central connections, and undergoes substantial cell loss. In this study, we describe the development of the retinal ganglion cell layer with particular attention to the creation of local specializations in cell density. Changes in the number and spatial distribution of cells identified by a single 3H thymidine injection were examined through the period of maximal cell loss (postnatal days 4-10) and at adulthood. The cells of the retinal ganglion cell layer are generated from embryonic day 10 to postnatal day 3. Overall, cell number in the ganglion cell layer increases by approximately 108,000 cells (223%) from postnatal day 1 to 5, because of continued migration of cells generated prenatally. Cell number decreases from postnatal day 5 to 10 (25%), coincident with the presence of degenerating cells. Cell type is correlated with day of generation: the largest cells, all having retinal ganglion cell morphology, are generated on embryonic days 10 and 11; intermediate-sized cells predominantly of ganglion cell morphology on embryonic day 12; and smaller cells of displaced amacrine or glial cell morphology thereafter. At adulthood, the hamster retina shows a streaklike elevation of cell density through central retina. However, at the time of maximal cell number (postnatal day 5), cell density is uniform across the retina. During the period of cell degeneration, cells are lost in greater relative numbers from the retinal periphery. This cell loss occurs principally from the first-generated cells (embryonic days 10 and 11), as shown by both changes in the distribution of labeled cells and by the spatial pattern of labeled degenerating cells. From postnatal day 10 to adulthood, relative cell density continues to decline in the periphery of the retina, thus suggesting that differential growth completes the production of the adult cell density distribution.

Animals↗